80 results on '"Weiyang Sun"'
Search Results
2. A live attenuated influenza B virus vaccine expressing RBD elicits protective immunity against SARS-CoV-2 in mice
- Author
-
Zhenfei Wang, Weiyang Sun, Dongxu Li, Yue Sun, Menghan Zhu, Wenqi Wang, Yiming Zhang, Entao Li, Feihu Yan, Tiecheng Wang, Na Feng, Songtao Yang, Xianzhu Xia, and Yuwei Gao
- Subjects
SARS-CoV-2 ,Influenza virus-vector vaccine ,Spike RBD ,Intranasal vaccination ,Mice ,Microbiology ,QR1-502 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a significant threat to human health globally. It is crucial to develop a vaccine to reduce the effect of the virus on public health, economy, and society and regulate the transmission of SARS-CoV-2. Influenza B virus (IBV) can be used as a vector that does not rely on the current circulating influenza A strains. In this study, we constructed an IBV-based vector vaccine by inserting a receptor-binding domain (RBD) into a non-structural protein 1 (NS1)-truncated gene (rIBV-NS110-RBD). Subsequently, we assessed its safety, immunogenicity, and protective efficacy against SARS-CoV-2 in mice, and observed that it was safe in a mouse model. Intranasal administration of a recombinant rIBV-NS110-RBD vaccine induced high levels of SARS-CoV-2-specific IgA and IgG antibodies and T cell-mediated immunity in mice. Administering two doses of the intranasal rIBV-NS110-RBD vaccine significantly reduced the viral load and lung damage in mice. This novel IBV-based vaccine offers a novel approach for controlling the SARS-CoV-2 pandemic.
- Published
- 2024
- Full Text
- View/download PDF
3. A potential Chinese medicine monomer against influenza A virus and influenza B virus: isoquercitrin
- Author
-
Rongbo Luo, Chaoxiang Lv, Tiecheng Wang, Xiuwen Deng, Mingwei Sima, Jin Guo, Jing Qi, Weiyang Sun, Beilei Shen, Yuanguo Li, Donghui Yue, and Yuwei Gao
- Subjects
Influenza A virus ,Influenza B virus ,Chinese medicine monomer ,Isoquercitrin ,Cytokines ,NF-κB signaling ,Other systems of medicine ,RZ201-999 - Abstract
Abstract Background Influenza viruses, especially Influenza A virus and Influenza B virus, are respiratory pathogens and can cause seasonal epidemics and pandemics. Severe influenza viruses infection induces strong host-defense response and excessive inflammatory response, resulting in acute lung damage, multiple organ failure and high mortality. Isoquercitrin is a Chinese medicine monomer, which was reported to have multiple biological activities, including antiviral activity against HSV, IAV, SARS-CoV-2 and so on. Aims of this study were to assess the in vitro anti-IAV and anti-IBV activity, evaluate the in vivo protective efficacy against lethal infection of the influenza virus and searched for the more optimal method of drug administration of isoquercitrin. Methods In vitro infection model (MDCK and A549 cells) and mouse lethal infection model of Influenza A virus and Influenza B virus were used to evaluate the antiviral activity of isoquercitrin. Results Isoquercitrin could significantly suppress the replication in vitro and in vivo and reduced the mortality of mouse lethal infection models. Compared with virus infection group, isoquercitrin mitigated lung and multiple organ damage. Moreover, isoquercitrin blocked hyperproduction of cytokines induced by virus infection via inactivating NF-κB signaling. Among these routes of isoquercitrin administration, intramuscular injection is a better drug delivery method. Conclusion Isoquercitrin is a potential Chinese medicine monomer Against Influenza A Virus and Influenza B Virus infection.
- Published
- 2023
- Full Text
- View/download PDF
4. Spatial Vulnerability Assessment for Mountain Cities Based on the GA-BP Neural Network: A Case Study in Linzhou, Henan, China
- Author
-
Yutong Duan, Miao Yu, Weiyang Sun, Shiyang Zhang, and Yunyuan Li
- Subjects
spatial vulnerability ,ecological wisdom ,BP neural network ,genetic algorithm (GA) ,mountain city ,Agriculture - Abstract
Mountain cities with complex topographies have always been highly vulnerable areas to global environmental change, prone to geological hazards, climate change, and human activities. Exploring and analyzing the vulnerability of coupling systems in mountain cities is highly important for improving regional resilience and promoting sustainable regional development. Therefore, a comprehensive framework for assessing the spatial vulnerability of mountain cities is proposed. A vulnerability assessment index system is constructed using three functional systems, ecological protection, agricultural production, and urban construction. Subsequently, the BP neural network and the genetic algorithm (GA) are combined to establish a vulnerability assessment model, and geographically weighted regression (GWR) is introduced to analyze the spatial influence of one-dimensional systems on the coupling system. Linzhou, a typical mountain city at the boundary between China’s second- and third-step terrains, was selected as a case study to demonstrate the feasibility of the framework. The results showed that the vulnerability of the ecological protection system was highly aggregated in the east–central region, that of the agricultural production system was high in the west, and that of the urban construction system was low in the central region and high in the northwestern region. The coupling system vulnerability was characterized by multispatial distribution. The complex topography and geomorphology and the resulting natural hazards are the underlying causes of the vulnerability results. The impact of ecological and urban systems on the coupling system vulnerability is more prominent. The proposed framework can serve as a reference for vulnerability assessments of other similar mountain cities with stepped topographies to support the formulation of sustainable development strategies.
- Published
- 2024
- Full Text
- View/download PDF
5. Cross-species infection potential of avian influenza H13 viruses isolated from wild aquatic birds to poultry and mammals
- Author
-
Weiyang Sun, Menglin Zhao, Zhijun Yu, Yuanguo Li, Xinghai Zhang, Na Feng, Tiecheng Wang, Hongmei Wang, Hongbin He, Yongkun Zhao, Songtao Yang, Xianzhu Xia, and Yuwei Gao
- Subjects
Avian influenza virus ,H13 ,wild aquatic birds ,poultry ,mice ,Infectious and parasitic diseases ,RC109-216 ,Microbiology ,QR1-502 - Abstract
ABSTRACTWild aquatic birds are the primary hosts of H13 avian influenza viruses (AIVs). Herein, we performed a genetic analysis of two H13 AIVs isolated from wild birds in China and evaluated their infection potential in poultry to further explore the potential for transmission from wild aquatic birds to poultry. Our results showed that the two strains belong to different groups, one strain (A/mallard/Dalian/DZ-137/2013; abbreviated as DZ137) belongs to Group I, whereas the other strain (A/Eurasian Curlew/Liaoning/ZH-385/2014; abbreviated as ZH385) belongs to Group III. In vitro experiments showed that both DZ137 and ZH385 can replicate efficiently in chicken embryo fibroblast cells. We found that these H13 AIVs can also efficiently replicate in mammalian cell lines, including human embryonic kidney cells and Madin-Darby canine kidney cells. In vivo experiments showed that DZ137 and ZH385 can infect 1-day-old specific pathogen-free (SPF) chickens, and that ZH385 has a higher replication ability in chickens than DZ137. Notably, only ZH385 can replicate efficiently in 10-day-old SPF chickens. However, neither DZ137 nor ZH385 can replicate well in turkeys and quails. Both DZ137 and ZH385 can replicate in 3-week-old mice. Serological surveillance of poultry showed a 4.6%-10.4% (15/328-34/328) antibody-positive rate against H13 AIVs in farm chickens. Our findings indicate that H13 AIVs have the replication ability in chickens and mice and may have a risk of crossing the host barrier from wild aquatic birds to poultry or mammals in the future.
- Published
- 2023
- Full Text
- View/download PDF
6. A novel hACE2 knock-in mouse model recapitulates pulmonary and intestinal SARS-CoV-2 infection
- Author
-
Xiaoyang Zhou, Weiyang Sun, Yu Zhang, Hongjing Gu, Ruixuan Wang, Peng Xie, Yunkai Zhu, Minyue Qiu, Xiaoyan Ding, Hui Wang, Yuwei Gao, and Jintao Li
- Subjects
mouse model ,intestinal infection ,SARS-CoV-2 ,immune cells ,pneumonia ,Microbiology ,QR1-502 - Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission is responsible for the coronavirus disease 2019 (COVID-19) pandemic. SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) receptor to enter the host, and the gastrointestinal tract is a potential infection site as this receptor is expressed on it. Multiple studies have indicated that an increasing number of COVID-19 patients presented with gastrointestinal symptoms that are highly associated with disease severity. Moreover, emerging evidence has demonstrated that alterations in the gut immune microenvironment induced by intestinal SARS-CoV-2 infection can regulate respiratory symptoms. Therefore, targeting the intestines may be a candidate therapeutic strategy in patients with COVID-19; however, no mouse model can serve as an appropriate infection model for the development of fatal pneumonia while mimicking intestinal infection. In this study, a novel human ACE2 knock-in (KI) mouse model (or hACE2-KI) was systemically compared with the popular K18-hACE2 mice; it showed differences in the distribution of lung and intestinal infections and pathophysiological characteristics. These newly generated hACE2-KI mice were susceptible to intranasal infection with SARS-CoV-2, and not only developed mild to severe lung injury, but also acquired intestinal infection. Consequently, this model can be a useful tool for studying intestinal SARS-CoV-2 infection and developing effective therapeutic strategies.
- Published
- 2023
- Full Text
- View/download PDF
7. Amino acid sites related to the PB2 subunits of IDV affect polymerase activity
- Author
-
Yutian Wang, Weiyang Sun, Zhenfei Wang, Menglin Zhao, Xinghai Zhang, Yunyi Kong, Xuefeng Wang, Na Feng, Tiecheng Wang, Feihu Yan, Yongkun Zhao, Xianzhu Xia, Songtao Yang, and Yuwei Gao
- Subjects
Influenza D virus ,Viral polymerase ,PB2 protein ,Single-site mutation ,Random mutation library ,Mini-replicon reporter constructs ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background In 2011, a new influenza virus, named Influenza D Virus (IDV), was isolated from pigs, and then cattle, presenting influenza-like symptoms. IDV is one of the causative agents of Bovine Respiratory Disease (BRD), which causes high morbidity and mortality in feedlot cattle worldwide. To date, the molecular mechanisms of IDV pathogenicity are unknown. Recent IDV outbreaks in cattle, along with serological and genetic evidence of IDV infection in humans, have raised concerns regarding the zoonotic potential of this virus. Influenza virus polymerase is a determining factor of viral pathogenicity to mammals. Methods Here we take a prospective approach to this question by creating a random mutation library about PB2 subunit of the IDV viral polymerase to test which amino acid point mutations will increase viral polymerase activity, leading to increased pathogenicity of the virus. Results Our work shows some exact sites that could affect polymerase activities in influenza D viruses. For example, two single-site mutations, PB2-D533S and PB2-G603Y, can independently increase polymerase activity. The PB2-D533S mutation alone can increase the polymerase activity by 9.92 times, while the PB2-G603Y mutation increments the activity by 8.22 times. Conclusion Taken together, our findings provide important insight into IDV replication fitness mediated by the PB2 protein, increasing our understanding of IDV replication and pathogenicity and facilitating future studies.
- Published
- 2021
- Full Text
- View/download PDF
8. PB1 S524G mutation of wild bird-origin H3N8 influenza A virus enhances virulence and fitness for transmission in mammals
- Author
-
Xinghai Zhang, Yuanguo Li, Song Jin, Yiming Zhang, Leiyun Sun, Xinyu Hu, Menglin Zhao, Fangxu Li, Tiecheng Wang, Weiyang Sun, Na Feng, Hongmei Wang, Hongbin He, Yongkun Zhao, Songtao Yang, Xianzhu Xia, and Yuwei Gao
- Subjects
Wild birds ,H3N8 influenza virus ,mammals ,transmission ,molecular basis ,Infectious and parasitic diseases ,RC109-216 ,Microbiology ,QR1-502 - Abstract
Influenza H3N8 viruses have been recovered frequently from wild bird species, including Anseriformes (primarily from migratory ducks) and Charadriiformes (primarily from shorebirds). However, little attention has been given to the transmission ability of H3N8 avian influenza viruses among mammals. Here, we study the potential human health threat and the molecular basis of mammalian transmissibility of H3N8 avian influenza viruses isolated from wild bird reservoirs. We classified eight H3N8 viruses into seven different genotypes based on genomic diversity. Six of eight H3N8 viruses isolated naturally from wild birds have acquired the ability to bind to the human-type receptor. However, the affinity for α-2,6-linked SAs was lower than that for α-2,3-linked SAs. Experiments on guinea pigs demonstrated that three viruses transmitted efficiently to direct-contact guinea pigs without prior adaptation. Notably, one virus transmitted efficiently via respiratory droplets in guinea pigs but not in ferrets. We further found that the PB1 S524G mutation conferred T222 virus airborne transmissibility between ferrets. We also determined that the 524G mutant increased viral pathogenicity slightly in mice compared with the WT (wild type). Based on these results, we elucidated the potential human health threat and molecular basis of mammalian transmissibility of H3N8 influenza viruses. We emphasized the need for continued surveillance of the H3N8 influenza viruses circulating in birds.
- Published
- 2021
- Full Text
- View/download PDF
9. Antibiotic resistance in patients with clinical features of healthcare-associated infections in an urban tertiary hospital in Sierra Leone: a cross-sectional study
- Author
-
Sulaiman Lakoh, Letian Li, Stephen Sevalie, Xuejun Guo, Olukemi Adekanmbi, Guang Yang, Oladimeji Adebayo, Le Yi, Joshua M. Coker, Shuchao Wang, Tiecheng Wang, Weiyang Sun, Abdulrazaq G. Habib, and Eili Y. Klein
- Subjects
Antibiotic resistance/stewardship/ bacteria/ diagnostic infrastructure ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Available data on antibiotic resistance in sub-Saharan Africa is limited despite its increasing threat to global public health. As there is no previous study on antibiotic resistance in patients with clinical features of healthcare-associated infections (HAIs) in Sierra Leone, research is needed to inform public health policies. Our study aimed to assess antibiotic resistance rates from isolates in the urine and sputum samples of patients with clinical features of HAIs. Methodology We conducted a cross-sectional study of adult inpatients aged ≥18 years at Connaught Hospital, an urban tertiary care hospital in Freetown between February and June 2018. Results Over the course of the study, we enrolled 164 patients. Risk factors for HAIs were previous antibiotic use (93.3%), comorbidities (58.5%) and age (≥65 years) (23.9%). Of the 164 samples, 89.6% were urine. Bacterial growth was recorded in 58.8% of cultured specimens; the type of specimen was an independent predictor of bacterial growth (p
- Published
- 2020
- Full Text
- View/download PDF
10. Neutralization activity of influenza A virus humanized antibodies against new subtypes of influenza viruses
- Author
-
Jing Liu, Tiecheng Wang, Ying Xie, Yuanguo Li, Jian He, Xinghai Zhang, Weiyang Sun, Na Feng, Chuan Qin, Yuwei Gao, and Xianzhu Xia
- Subjects
Influenza A virus humanized antibodies ,Neutralization activity ,New subtypes of influenza viruses ,Infectious and parasitic diseases ,RC109-216 ,Public aspects of medicine ,RA1-1270 - Abstract
Antibodies are ideal for controlling the influenza A virus, but their effect on newly emerging strains is unclear. Here, we assessed the neutralization activity of the humanized monoclonal antibodies (mAbs) F10, H98 and H40 against circulating influenza viruses (H5N1, H1N1, H3N2 and H7N7 and new subtypes viruses H5N6 and H7N9). The results showed that all the three humanized mAbs (F10, H98 and H40) displayed different degrees of virus neutralization activities when encountered with different subtypes of influenza viruses. Remarkably, the humanized monoclonal antibody F10 produced higher and broader neutralization titers (range 25–1.56 μg/ml) than those of the other two humanized mAbs (H98 (range 50–3.12 μg/ml), H40 (range 50–5.56 μg/ml)) to against the viruses H5N1, H1N1, H3N2, H7N7, H5N6 and H7N9. This mAb may represent a new class of heterosubtypic neutralizing humanized mAb that could replace vaccines and chemical drugs.
- Published
- 2019
- Full Text
- View/download PDF
11. Safety, Immunogenicity, and Protective Efficacy of an H5N1 Chimeric Cold-Adapted Attenuated Virus Vaccine in a Mouse Model
- Author
-
Weiyang Sun, Zhenfei Wang, Yue Sun, Dongxu Li, Menghan Zhu, Menglin Zhao, Yutian Wang, Jiaqi Xu, Yunyi Kong, Yuanguo Li, Na Feng, Tiecheng Wang, Yongkun Zhao, Songtao Yang, Yuwei Gao, and Xianzhu Xia
- Subjects
H5N1 influenza virus ,chimeric vaccine ,mice ,immune protection ,Microbiology ,QR1-502 - Abstract
H5N1 influenza virus is a threat to public health worldwide. The virus can cause severe morbidity and mortality in humans. We constructed an H5N1 influenza candidate virus vaccine from the A/chicken/Guizhou/1153/2016 strain that was recommended by the World Health Organization. In this study, we designed an H5N1 chimeric influenza A/B vaccine based on a cold-adapted (ca) influenza B virus B/Vienna/1/99 backbone. We modified the ectodomain of H5N1 hemagglutinin (HA) protein, while retaining the packaging signals of influenza B virus, and then rescued a chimeric cold-adapted H5N1 candidate influenza vaccine through a reverse genetic system. The chimeric H5N1 vaccine replicated well in eggs and the Madin-Darby Canine Kidney cells. It maintained a temperature-sensitive and cold-adapted phenotype. The H5N1 vaccine was attenuated in mice. Hemagglutination inhibition (HAI) antibodies, micro-neutralizing (MN) antibodies, and IgG antibodies were induced in immunized mice, and the mucosal IgA antibody responses were detected in their lung lavage fluids. The IFN-γ-secretion and IL-4-secretion by the mouse splenocytes were induced after stimulation with the specific H5N1 HA protein. The chimeric H5N1 candidate vaccine protected mice against lethal challenge with a wild-type highly pathogenic avian H5N1 influenza virus. The chimeric H5 candidate vaccine is thus a potentially safe, attenuated, and reassortment-incompetent vaccine with circulating A viruses.
- Published
- 2021
- Full Text
- View/download PDF
12. Characterization of Canine Influenza Virus A (H3N2) Circulating in Dogs in China from 2016 to 2018
- Author
-
Yuanguo Li, Xinghai Zhang, Yuxiu Liu, Ye Feng, Tiecheng Wang, Ye Ge, Yunyi Kong, Hongyu Sun, Haiyang Xiang, Bo Zhou, Shushan Fang, Qing Xia, Xinyu Hu, Weiyang Sun, Xuefeng Wang, Keyin Meng, Chaoxiang Lv, Entao Li, Xianzhu Xia, Hongbin He, Yuwei Gao, and Ningyi Jin
- Subjects
canine influenza virus ,evolution ,serological surveillance ,transmission ,Microbiology ,QR1-502 - Abstract
Avian H3N2 influenza virus follows cross-host transmission and has spread among dogs in Asia since 2005. After 2015–2016, a new H3N2 subtype canine influenza epidemic occurred in dogs in North America and Asia. The disease prevalence was assessed by virological and serological surveillance in dogs in China. Herein, five H3N2 canine influenza virus (CIV) strains were isolated from 1185 Chinese canine respiratory disease samples in 2017–2018; these strains were on the evolutionary branch of the North American CIVs after 2016 and genetically far from the classical canine H3N2 strain discovered in China before 2016. Serological surveillance showed an HI antibody positive rate of 6.68%. H3N2 was prevalent in the coastal areas and northeastern regions of China. In 2018, it became the primary epidemic strain in the country. The QK01 strain of H3N2 showed high efficiency in transmission among dogs through respiratory droplets. Nevertheless, the virus only replicated in the upper respiratory tract and exhibited low pathogenicity in mice. Furthermore, highly efficient transmission by direct contact other than respiratory droplet transmission was found in a guinea pig model. The low-level replication in avian species other than ducks could not facilitate contact and airborne transmission in chickens. The current results indicated that a novel H3N2 virus has become a predominant epidemic strain in dogs in China since 2016 and acquired highly efficient transmissibility but could not be replicated in avian species. Thus, further monitoring is required for designing optimal immunoprophylactic tools for dogs and estimating the zoonotic risk of CIV in China.
- Published
- 2021
- Full Text
- View/download PDF
13. Characteristics of Chimeric West Nile Virus Based on the Japanese Encephalitis Virus SA14-14-2 Backbone
- Author
-
Guohua Li, Xianyong Meng, Zhiguang Ren, Entao Li, Feihu Yan, Jing Liu, Ying Zhang, Zhanding Cui, Yuetao Li, Hongli Jin, Zengguo Cao, Le Yi, Pei Huang, Hang Chi, Hualei Wang, Weiyang Sun, Tiecheng Wang, Yuwei Gao, Yongkun Zhao, Songtao Yang, and Xianzhu Xia
- Subjects
Japanese encephalitis virus ,West Nile virus ,chimera ,Microbiology ,QR1-502 - Abstract
West Nile virus disease (WND) is an arthropod-borne zoonosis responsible for nonspecific fever or severe encephalitis. The pathogen is West Nile virus belonging to the genus Flavivirus, family Flaviviridae. Every year, thousands of cases were reported, which poses significant public health risk. Here, we constructed a West Nile virus chimera, ChiVax-WN01, by replacing the prMΔE gene of JEV SA14-14-2 with that of the West Nile virus NY99. The ChiVax-WN01 chimera showed clear, different characters compared with that of JEV SA14-14-2 and WNV NY99 strain. An animal study indicated that the ChiVax-WN01 chimera presented moderate safety and immunogenicity for 4-week female BALB/c mice.
- Published
- 2021
- Full Text
- View/download PDF
14. A Rapid and Specific Assay for the Detection of MERS-CoV
- Author
-
Pei Huang, Hualei Wang, Zengguo Cao, Hongli Jin, Hang Chi, Jincun Zhao, Beibei Yu, Feihu Yan, Xingxing Hu, Fangfang Wu, Cuicui Jiao, Pengfei Hou, Shengnan Xu, Yongkun Zhao, Na Feng, Jianzhong Wang, Weiyang Sun, Tiecheng Wang, Yuwei Gao, Songtao Yang, and Xianzhu Xia
- Subjects
Middle East respiratory syndrome coronavirus ,reverse transcription loop-mediated isothermal amplification ,nucleic acid visualization ,visual detection ,RT-LAMP-VF ,Microbiology ,QR1-502 - Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel human coronavirus that can cause human respiratory disease. The development of a detection method for this virus that can lead to rapid and accurate diagnosis would be significant. In this study, we established a nucleic acid visualization technique that combines the reverse transcription loop-mediated isothermal amplification technique and a vertical flow visualization strip (RT-LAMP-VF) to detect the N gene of MERS-CoV. The RT-LAMP-VF assay was performed in a constant temperature water bath for 30 min, and the result was visible by the naked eye within 5 min. The RT-LAMP-VF assay was capable of detecting 2 × 101 copies/μl of synthesized RNA transcript and 1 × 101 copies/μl of MERS-CoV RNA. The method exhibits no cross-reactivities with multiple CoVs including SARS-related (SARSr)-CoV, HKU4, HKU1, OC43 and 229E, and thus exhibits high specificity. Compared to the real-time RT-PCR (rRT-PCR) method recommended by the World Health Organization (WHO), the RT-LAMP-VF assay is easy to handle, does not require expensive equipment and can rapidly complete detection within 35 min.
- Published
- 2018
- Full Text
- View/download PDF
15. Genetically Modified Rabies Virus Vector-Based Rift Valley Fever Virus Vaccine is Safe and Induces Efficacious Immune Responses in Mice
- Author
-
Shengnan Zhang, Meng Hao, Na Feng, Hongli Jin, Feihu Yan, Hang Chi, Hualei Wang, Qiuxue Han, Jianzhong Wang, Gary Wong, Bo Liu, Jun Wu, Yuhai Bi, Tiecheng Wang, Weiyang Sun, Yuwei Gao, Songtao Yang, Yongkun Zhao, and Xianzhu Xia
- Subjects
rift valley fever virus ,rabies virus ,inactivated vaccine ,rvfv-specific igg antibodies ,adjuvant ,Microbiology ,QR1-502 - Abstract
Rift Valley fever virus (RVFV), which causes Rift Valley fever (RVF), is a mosquito-borne zoonotic pathogen that causes serious morbidity and mortality in livestock and humans. RVF is a World Health Organization (WHO) priority disease and, together with rabies, is a major health burden in Africa. Here, we present the development and characterization of an inactivated recombinant RVFV and rabies virus (RABV) vaccine candidate (rSRV9-eGn). Immunization with rSRV9-eGn stimulated the production of RVFV-specific IgG antibodies and induced humoral and cellular immunity in mice but did not induce the production of neutralizing antibodies. IgG1 and IgG2a were the main isotypes observed by IgG subtype detection, and IgG3 antibodies were not detected. The ratios of IgG1/IgG2a > 1 indicated a Type 2 humoral immune response. An effective vaccine is intended to establish a long-lived population of memory T cells, and mice generated memory cells among the proliferating T cell population after immunization with rSRV9-eGn, with effector memory T cells (TEM) as the major population. Due to the lack of prophylactic treatment experiments, it is impossible to predict whether this vaccine can protect animals from RVFV infection with only high titres of anti-RVFV IgG antibodies and no neutralizing antibodies induced, and thus, protection confirmation needs further verification. However, this RVFV vaccine designed with RABV as the vector provides ideas for the development of vaccines that prevent RVFV and RABV infections.
- Published
- 2019
- Full Text
- View/download PDF
16. A Novel Bacterium-Like Particle Vaccine Displaying the MERS-CoV Receptor-Binding Domain Induces Specific Mucosal and Systemic Immune Responses in Mice
- Author
-
Entao Li, Hang Chi, Pei Huang, Feihu Yan, Ying Zhang, Chuanyu Liu, Zhenshan Wang, Guohua Li, Shengnan Zhang, Ruo Mo, Hongli Jin, Hualei Wang, Na Feng, Jianzhong Wang, Yuhai Bi, Tiecheng Wang, Weiyang Sun, Yuwei Gao, Yongkun Zhao, Songtao Yang, and Xianzhu Xia
- Subjects
MERS-CoV ,subunit vaccine ,bacterium-like particles ,intranasal administration ,mucosal immune ,Microbiology ,QR1-502 - Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV), a new coronavirus that has been causing severe and fatal acute respiratory illnesses in humans since its outbreak in 2012, has raised public fear worldwide. The development of prophylactics and therapeutics is urgently needed to prevent and control MERS-CoV infections. In this study, a bacterium (Lactococcus lactis)-like particle (BLP) vaccine displaying the MERS-CoV receptor-binding domain (RBD) was developed, and gram-positive enhancer matrix (GEM) particles were used as substrates to externally bind to the MERS-CoV RBD through a protein anchor (PA). The designs included different numbers of lysin motif (LysM) repeats in the PAs linked by linkers (RBD-linker-PA2 (RLP2), RBD-linker-PA3 (RLP3) and RBD-PA3 (RP3)), and three LysM repeats and a linker in the fusion proteins increased the binding activity to the RBD. The specific immune responses were tested by intranasally immunizing mice with RLP3-GEM with or without the adjuvant GEL01. The results showed that GEL01-adjuvanted RLP3-GEM increased the systemic humoral, cellular and local mucosal immune responses in the mouse model, especially in the intestinal tract. The above results indicate that the MERS-CoV BLP product has the potential to be developed into a promising mucosal candidate vaccine to protect against MERS-CoV infections.
- Published
- 2019
- Full Text
- View/download PDF
17. Image Encryption Performance Evaluation Based on Poker Test
- Author
-
Shanshan Li and Weiyang Sun
- Subjects
Electronic computers. Computer science ,QA75.5-76.95 - Abstract
The fast development of image encryption requires performance evaluation metrics. Traditional metrics like entropy do not consider the correlation between local pixel and its neighborhood. These metrics cannot estimate encryption based on image pixel coordinate permutation. A novel effectiveness evaluation metric is proposed in this paper to address the issue. The cipher text image is transformed to bit stream. Then, Poker Test is implemented. The proposed metric considers the neighbor correlations of image by neighborhood selection and clip scan. The randomness of the cipher text image is tested by calculating the chi-square test value. Experiment results verify the efficiency of the proposed metrics.
- Published
- 2016
- Full Text
- View/download PDF
18. Topology Reconstruction of Heterogeneous Networked Dynamical Systems with Unknown Input Matrices.
- Author
-
Weiyang Sun, Jinming Xu 0002, and Jiming Chen 0001
- Published
- 2024
- Full Text
- View/download PDF
19. Equine Immunoglobulin and Equine Neutralizing F(ab′)2 Protect Mice from West Nile Virus Infection
- Author
-
Jiannan Cui, Yongkun Zhao, Hualei Wang, Boning Qiu, Zengguo Cao, Qian Li, Yanbo Zhang, Feihu Yan, Hongli Jin, Tiecheng Wang, Weiyang Sun, Na Feng, Yuwei Gao, Jing Sun, Yanqun Wang, Stanley Perlman, Jincun Zhao, Songtao Yang, and Xianzhu Xia
- Subjects
West Nile virus ,equine immunoglobulin ,F(ab′)2 fragments ,mice ,Microbiology ,QR1-502 - Abstract
West Nile virus (WNV) is prevalent in Africa, Europe, the Middle East, West Asia, and North America, and causes epidemic encephalitis. To date, no effective therapy for WNV infection has been developed; therefore, there is urgent need to find an efficient method to prevent WNV disease. In this study, we prepared and evaluated the protective efficacy of immune serum IgG and pepsin-digested F(ab′)2 fragments from horses immunized with the WNV virus-like particles (VLP) expressing the WNV M and E proteins. Immune equine F(ab′)2 fragments and immune horse sera efficiently neutralized WNV infection in tissue culture. The passive transfer of equine immune antibodies significantly accelerated the virus clearance in the spleens and brains of WNV infected mice, and reduced mortality. Thus, equine immunoglobulin or equine neutralizing F(ab′)2 passive immunotherapy is a potential strategy for the prophylactic or therapeutic treatment of patients infected with WNV.
- Published
- 2016
- Full Text
- View/download PDF
20. On Necessary and Sufficient Conditions for Identifiability and Identification of Switching Dynamical Networks.
- Author
-
Weiyang Sun, Jinming Xu 0002, and Jiming Chen 0001
- Published
- 2022
- Full Text
- View/download PDF
21. SARS-CoV-2 ORF8 Protein Induces Endoplasmic Reticulum Stress-like Responses and Facilitates Virus Replication by Triggering Calnexin: an Unbiased Study
- Author
-
Xuefeng Wang, Wenqi Wang, Tiecheng Wang, Jianzhong Wang, Yuhang Jiang, Xue Wang, Ze Qiu, Na Feng, Weiyang Sun, Chang Li, Songtao Yang, Xianzhu Xia, Hongbin He, and Yuwei Gao
- Subjects
Virology ,Insect Science ,Immunology ,Microbiology - Abstract
Although SARS-CoV-2 is basically regarded as a homolog of SARS-CoV, with their genomic structure and the majority of their genes being highly homologous, the ORF8 genes of SARS-CoV and SARS-CoV-2 are distinct. The SARS-CoV-2 ORF8 protein also shows little homology with other viral or host proteins and is thus regarded as a novel special virulence gene of SARS-CoV-2.
- Published
- 2023
22. Clade 2.3.4.4 H5 chimeric cold-adapted attenuated influenza vaccines induced cross-reactive protection in mice and ferrets.
- Author
-
Weiyang Sun, Jiaqi Xu, Zhenfei Wang, Dongxu Li, Yue Sun, Menghan Zhu, Xiawei Liu, Yuanguo Li, Fangxu Li, Tiecheng Wang, Na Feng, Zhendong Guo, Xianzhu Xia, and Yuwei Gao
- Subjects
- *
MICE , *INFLUENZA vaccines , *AVIAN influenza A virus , *FERRET , *INFLUENZA B virus , *INFLUENZA A virus - Abstract
Clade 2.3.4.4 H5Nx subtype avian influenza viruses (AIVs) have circulated in poultry and wild birds worldwide. Recently, an increasing number of H5Nx human infection cases have been reported occurred. Live attenuated influenza vaccines demonstrate more advantages than other types of vaccines, such as ease of administration, elicitation of systemic immune responses, and the ability to generate breadth protection. However, the attenuated viruses also bear the risk of reassortment with the wild-type influenza A virus. To overcome this reassortment problem, we designed and constructed Clade 2.3.4.4 H5 chimeric cold-adapted attenuated influenza vaccines (CAIVs) by introducing the hemagglutinin ectodomains of H5N6 into a cold-adapted attenuated master donor of an influenza B virus. These H5 CAIVs induce humoral antibody response, mucosal immune response, and cellular immune response in mice models. After two doses were administered in mice, H5 CAIVs provided cross-protection responses with 100% survival against wild-type Clade 2.3.4.4 H5 subtype AIVs. The immunized mice exhibited more significant reductions of lung viral titers or lung pathology than those in the mock group mice. In ferret models, Clade 2.3.4.4b and 2.3.4.4h H5 CAIVs produced a cross-protective efficacy against wild-type Clade 2.3.4.4b and Clade 2.3.4.4h H5 AIVs. The findings of the current study indicate that our H5 CAIVs may have the potential to prevent and control H5Nx influenza viruses in humans. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
23. Bandage contact lens soaked in 0.1% diclofenac to relieve early postoperative pain and foreign body sensation after transepithelial photorefractive keratectomy
- Author
-
Yuan Wang, Fei Shen, Weiyang Sun, Qinmei Wang, and Xiangyang Zhao
- Subjects
Pain, Postoperative ,Ophthalmology ,Diclofenac ,Myopia ,Sensation ,Humans ,Lasers, Excimer ,Prospective Studies ,General Medicine ,Foreign Bodies ,Bandages ,Photorefractive Keratectomy - Abstract
Purpose To study the effects of a bandage contact lens immersed in 0.1% diclofenac on pain management for patients undergoing transepithelial photorefractive keratectomy (TPRK). Methods In a prospective, comparative, contralateral, randomized, double-masked study, we assessed a total of 51 patients. The eyes of each patient were randomly divided into two groups. After TPRK, a normal soft bandage contact lens was placed on one eye as the control group, and a bandage contact lens soaked in diclofenac was placed on the other eye as the experimental group. When the bandage contact lens was not removed, postoperative pain and other ocular discomforts were compared at 2, 18, and 24 h and 2, 3, 4, and 5 postoperative days. Patients were then examined after 1 month. Visual acuity and subepithelial haze were also evaluated. Results The mean pain score was 2.69 ± 1.96 in the control group, which was significantly higher than that in the experimental group, which received the diclofenac-soaked bandage contact lens at 2 postoperative hours. The statistical difference between the two groups’ mean foreign body sensation at 2 postoperative hours was detected (p = 0.035). No differences were detected between the two groups’ subepithelial haze scores or visual acuity. Conclusion A bandage contact lens soaked in 0.1% diclofenac solution can be used as a potential drug-delivery system to relieve early postoperative pain and foreign body sensation after TPRK.
- Published
- 2022
24. A A212T Substitution in Hemagglutinin Impacts on the Rescue of Influenza A(H1N1)/B Chimeric Live-Attenuated Vaccine Candidate
- Author
-
Menglin ZHAO, Weiyang SUN, Dongxu LI, Xiawei LIU, Yue SUN, Menghan ZHU, Tiecheng WANG, Xianzhu XIA, and Yuwei GAO
- Abstract
The influenza virus, a viral respiratory pathogen, causes major morbidity and mortality worldwide. In this study, we compared and analyzed the effectiveness of the rescued two chimeric H1N1 vaccine strains rA/B-California/04/2009 and rA/B-California/07/2009, respectively, which expressed the hemagglutinin of A/California/07/2009 or A/California/04/2009 based on an influenza B virus master donor. The rA/B-California/07/2009 strain was rescued successfully. However, the rA/B-California/04/2009, which expressed the HA of A/California/07/2009 could hardly be generated. In substitution for alanine at residue 212 in the chimeric HA protein of rA/B-California/04/2009 virus, threonine was identified as a deleterious change. The free Gibbs energy change of mutating residue 212 reflected that threonine in site 212 caused a reduction in the stability of rA/B-California HAs. Additionally, with the analysis of binding free energy data and RMSD values of receptor analogs and two chimeric HAs, substitution 212T also conferred decreased receptor-binding avidity. These results suggested that the substitution A212T may enhance the stability and binding affinity of the chimeric H1N1 vaccine strains. This finding may help to design a live-attenuated influenza vaccine with more efficacy.
- Published
- 2023
25. PB1 S524G mutation of wild bird-origin H3N8 influenza A virus enhances virulence and fitness for transmission in mammals
- Author
-
Yongkun Zhao, Leiyun Sun, Fangxu Li, Hongbin He, Li Yuanguo, Song Jin, Xianzhu Xia, Tiecheng Wang, Na Feng, Menglin Zhao, Hongmei Wang, Yuwei Gao, Xinyu Hu, Yiming Zhang, Songtao Yang, Xinghai Zhang, and Weiyang Sun
- Subjects
0301 basic medicine ,Genotype ,Epidemiology ,viruses ,Guinea Pigs ,030106 microbiology ,Immunology ,Virulence ,medicine.disease_cause ,H3N8 influenza virus ,Polymorphism, Single Nucleotide ,Microbiology ,Virus ,Wild birds ,Madin Darby Canine Kidney Cells ,Influenza A Virus, H3N8 Subtype ,Mice ,Viral Proteins ,03 medical and health sciences ,Dogs ,Orthomyxoviridae Infections ,Virology ,Drug Discovery ,medicine ,Influenza A virus ,Animals ,Humans ,mammals ,biology ,Transmission (medicine) ,transmission ,Wild type ,General Medicine ,Anseriformes ,biology.organism_classification ,Influenza A virus subtype H5N1 ,molecular basis ,Disease Models, Animal ,030104 developmental biology ,Infectious Diseases ,Female ,Parasitology ,Genetic Fitness ,Research Article - Abstract
Influenza H3N8 viruses have been recovered frequently from wild bird species, including Anseriformes (primarily from migratory ducks) and Charadriiformes (primarily from shorebirds). However, little attention has been given to the transmission ability of H3N8 avian influenza viruses among mammals. Here, we study the potential human health threat and the molecular basis of mammalian transmissibility of H3N8 avian influenza viruses isolated from wild bird reservoirs. We classified eight H3N8 viruses into seven different genotypes based on genomic diversity. Six of eight H3N8 viruses isolated naturally from wild birds have acquired the ability to bind to the human-type receptor. However, the affinity for α-2,6-linked SAs was lower than that for α-2,3-linked SAs. Experiments on guinea pigs demonstrated that three viruses transmitted efficiently to direct-contact guinea pigs without prior adaptation. Notably, one virus transmitted efficiently via respiratory droplets in guinea pigs but not in ferrets. We further found that the PB1 S524G mutation conferred T222 virus airborne transmissibility between ferrets. We also determined that the 524G mutant increased viral pathogenicity slightly in mice compared with the WT (wild type). Based on these results, we elucidated the potential human health threat and molecular basis of mammalian transmissibility of H3N8 influenza viruses. We emphasized the need for continued surveillance of the H3N8 influenza viruses circulating in birds.
- Published
- 2021
26. Quantised output-feedback design for networked control systems using semi-Markov model approach
- Author
-
Zepeng Ning and Weiyang Sun
- Subjects
Output feedback ,Controller design ,0209 industrial biotechnology ,Computer science ,Linear system ,02 engineering and technology ,Markov model ,Stability (probability) ,Computer Science Applications ,Theoretical Computer Science ,020901 industrial engineering & automation ,Control and Systems Engineering ,Control theory ,Control system ,0202 electrical engineering, electronic engineering, information engineering ,020201 artificial intelligence & image processing ,Computer Science::Information Theory ,Communication channel - Abstract
This paper focuses on the stability analysis and controller design for a family of discrete-time linear systems with quantised signals in both control input channel and measurement output channel. ...
- Published
- 2020
27. Amino acid sites related to the PB2 subunits of IDV affect polymerase activity
- Author
-
Na Feng, Tiecheng Wang, Yunyi Kong, Yutian Wang, Feihu Yan, Xuefeng Wang, Yongkun Zhao, Songtao Yang, Xianzhu Xia, Xinghai Zhang, Zhenfei Wang, Menglin Zhao, Yuwei Gao, and Weiyang Sun
- Subjects
Swine ,Protein subunit ,viruses ,Bovine respiratory disease ,Single-site mutation ,Infectious and parasitic diseases ,RC109-216 ,medicine.disease_cause ,Virus Replication ,Virus ,Viral polymerase ,PB2 protein ,Orthomyxoviridae Infections ,Virology ,medicine ,Animals ,Mini-replicon reporter constructs ,Amino Acids ,Polymerase ,Mutation ,biology ,Point mutation ,Research ,Outbreak ,virus diseases ,medicine.disease ,biology.organism_classification ,Orthomyxoviridae ,Infectious Diseases ,biology.protein ,Random mutation library ,Cattle ,Thogotovirus ,Influenza D virus - Abstract
Background In 2011, a new influenza virus, named Influenza D Virus (IDV), was isolated from pigs, and then cattle, presenting influenza-like symptoms. IDV is one of the causative agents of Bovine Respiratory Disease (BRD), which causes high morbidity and mortality in feedlot cattle worldwide. To date, the molecular mechanisms of IDV pathogenicity are unknown. Recent IDV outbreaks in cattle, along with serological and genetic evidence of IDV infection in humans, have raised concerns regarding the zoonotic potential of this virus. Influenza virus polymerase is a determining factor of viral pathogenicity to mammals. Methods Here we take a prospective approach to this question by creating a random mutation library about PB2 subunit of the IDV viral polymerase to test which amino acid point mutations will increase viral polymerase activity, leading to increased pathogenicity of the virus. Results Our work shows some exact sites that could affect polymerase activities in influenza D viruses. For example, two single-site mutations, PB2-D533S and PB2-G603Y, can independently increase polymerase activity. The PB2-D533S mutation alone can increase the polymerase activity by 9.92 times, while the PB2-G603Y mutation increments the activity by 8.22 times. Conclusion Taken together, our findings provide important insight into IDV replication fitness mediated by the PB2 protein, increasing our understanding of IDV replication and pathogenicity and facilitating future studies.
- Published
- 2021
28. Taurolidine improved protection against highly pathogenetic avian influenza H5N1 virus lethal-infection in mouse model by regulating the NF-κB signaling pathway
- Author
-
Chaoxiang Lv, Yuanguo Li, Tiecheng Wang, Qiqi Zhang, Jing Qi, Mingwei Sima, Entao Li, Tian Qin, Zhuangzhuang Shi, Fangxu Li, Xuefeng Wang, Weiyang Sun, Na Feng, Songtao Yang, Xianzhu Xia, Ningyi Jin, Yifa Zhou, and Yuwei Gao
- Subjects
Virology ,Immunology ,Molecular Medicine - Abstract
Taurolidine (TRD), a derivative of taurine, has anti-bacterial and anti-tumor effects by chemically reacting with cell-walls, endotoxins and exotoxins to inhibit the adhesion of microorganisms. However, its application in antiviral therapy is seldom reported. Here, we reported that TRD significantly inhibited the replication of influenza virus H5N1 in MDCK cells with the half-maximal inhibitory concentration (EC
- Published
- 2021
29. The Application of a Safe Neutralization Assay for Ebola Virus Using Lentivirus-Based Pseudotyped Virus
- Author
-
Gary Wong, Fangfang Wu, Tiecheng Wang, Hongli Jin, Xianzhu Xia, Yang Songtao, Weiyang Sun, Zengguo Cao, Feng Na, Hualei Wang, Yongkun Zhao, Ying Zhang, Cuicui Jiao, Hang Chi, Yuwei Gao, and Shengnan Xu
- Subjects
medicine.medical_specialty ,Ebola virus ,Letter ,biology ,business.industry ,Immunology ,Genetic Vectors ,Lentivirus ,Hemorrhagic Fever, Ebola ,medicine.disease_cause ,biology.organism_classification ,Ebolavirus ,Virology ,Virus ,Neutralization ,Medical microbiology ,Neutralization Tests ,medicine ,Molecular Medicine ,Humans ,Viral Pseudotyping ,business - Published
- 2021
30. Viral and Host Transcriptomes in SARS-CoV-2-Infected Human Lung Cells
- Author
-
Hongmei Wang, Wenqi Wang, Weiyang Sun, Yuwei Gao, Xuefeng Wang, Xianzhu Xia, Hongbin He, Feihu Yan, Tiecheng Wang, Yudong Zhao, Na Feng, and Songtao Yang
- Subjects
viruses ,Immunology ,TNF ,transcription-regulating sequence ,030209 endocrinology & metabolism ,Biology ,Virus Replication ,Microbiology ,Genome ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,Transcription (biology) ,valine ,Virology ,Chlorocebus aethiops ,medicine ,Animals ,Humans ,RNA, Messenger ,Gene ,Lung ,Vero Cells ,Cells, Cultured ,030304 developmental biology ,Subgenomic mRNA ,0303 health sciences ,SARS-CoV-2 ,RNA ,COVID-19 ,cholesterol ,Epithelial Cells ,medicine.disease ,Cell biology ,Genome Replication and Regulation of Viral Gene Expression ,Viral replication ,Insect Science ,Cytokine storm - Abstract
Coronaviruses are commonly characterized by a unique discontinuous RNA transcriptional synthesis strategy guided by transcription-regulating sequences (TRSs). However, the details of RNA synthesis in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been fully elucidated. Here, we present a time-scaled, gene-comparable transcriptome of SARS-CoV-2, demonstrating that ACGAAC functions as a core TRS guiding the discontinuous RNA synthesis of SARS-CoV-2 from a holistic perspective. During infection, viral transcription, rather than genome replication, dominates all viral RNA synthesis activities. The most highly expressed viral gene is the nucleocapsid gene, followed by ORF7 and ORF3 genes, while the envelope gene shows the lowest expression. Host transcription dysregulation keeps exacerbating after viral RNA synthesis reaches a maximum. The most enriched host pathways are metabolism related. Two of them (cholesterol and valine metabolism) affect viral replication in reverse. Furthermore, the activation of numerous cytokines emerges before large-scale viral RNA synthesis. IMPORTANCE SARS-CoV-2 is responsible for the current severe global health emergency that began at the end of 2019. Although the universal transcriptional strategies of coronaviruses are preliminarily understood, the details of RNA synthesis, especially the time-matched transcription level of each SARS-CoV-2 gene and the principles of subgenomic mRNA synthesis, are not clear. The coterminal subgenomic mRNAs of SARS-CoV-2 present obstacles in identifying the expression of most genes by PCR-based methods, which are exacerbated by the lack of related antibodies. Moreover, SARS-CoV-2-related metabolic imbalance and cytokine storm are receiving increasing attention from both clinical and mechanistic perspectives. Our transcriptomic research provides information on both viral RNA synthesis and host responses, in which the transcription-regulating sequences and transcription levels of viral genes are demonstrated, and the metabolic dysregulation and cytokine levels identified at the host cellular level support the development of novel medical treatment strategies.
- Published
- 2021
31. Characteristics of Chimeric West Nile Virus Based on the Japanese Encephalitis Virus SA14-14-2 Backbone
- Author
-
Yuetao Li, Hang Chi, Weiyang Sun, Guohua Li, Yongkun Zhao, Zhanding Cui, Tiecheng Wang, Ying Zhang, Hongli Jin, Hualei Wang, Feihu Yan, Songtao Yang, Le Yi, Zhiguang Ren, Yuwei Gao, Entao Li, Jing Liu, Zengguo Cao, Xianyong Meng, Xian-Zhu Xia, and Pei Huang
- Subjects
0301 basic medicine ,West Nile virus ,viruses ,Biology ,medicine.disease_cause ,Microbiology ,Article ,Virus ,Cell Line ,chimera ,Mice ,03 medical and health sciences ,Chimera (genetics) ,0302 clinical medicine ,Cricetinae ,Virology ,medicine ,Animals ,030212 general & internal medicine ,Pathogen ,Encephalitis Virus, Japanese ,Mice, Inbred BALB C ,Virulence ,Immunogenicity ,Zoonosis ,virus diseases ,Japanese encephalitis ,medicine.disease ,QR1-502 ,Japanese encephalitis virus ,030104 developmental biology ,Infectious Diseases ,Female ,Encephalitis - Abstract
West Nile virus disease (WND) is an arthropod-borne zoonosis responsible for nonspecific fever or severe encephalitis. The pathogen is West Nile virus belonging to the genus Flavivirus, family Flaviviridae. Every year, thousands of cases were reported, which poses significant public health risk. Here, we constructed a West Nile virus chimera, ChiVax-WN01, by replacing the prMΔE gene of JEV SA14-14-2 with that of the West Nile virus NY99. The ChiVax-WN01 chimera showed clear, different characters compared with that of JEV SA14-14-2 and WNV NY99 strain. An animal study indicated that the ChiVax-WN01 chimera presented moderate safety and immunogenicity for 4-week female BALB/c mice.
- Published
- 2021
32. Neutralization activity of influenza A virus humanized antibodies against new subtypes of influenza viruses
- Author
-
Jian He, Jing Liu, Weiyang Sun, Na Feng, Yuwei Gao, Yuanguo Li, Xianzhu Xia, Chuan Qin, Xinghai Zhang, Ying Xie, and Tiecheng Wang
- Subjects
Microbiology (medical) ,medicine.drug_class ,Neutralization activity ,viruses ,Virus Neutralization ,medicine.disease_cause ,Monoclonal antibody ,Neutralization ,lcsh:Infectious and parasitic diseases ,New subtypes of influenza viruses ,Influenza A virus ,medicine ,lcsh:RC109-216 ,biology ,Influenza A virus humanized antibodies ,lcsh:Public aspects of medicine ,Public Health, Environmental and Occupational Health ,virus diseases ,lcsh:RA1-1270 ,Virology ,Influenza A virus subtype H5N1 ,Titer ,Infectious Diseases ,biology.protein ,Antibody ,Biotechnology - Abstract
Antibodies are ideal for controlling the influenza A virus, but their effect on newly emerging strains is unclear. Here, we assessed the neutralization activity of the humanized monoclonal antibodies (mAbs) F10, H98 and H40 against circulating influenza viruses (H5N1, H1N1, H3N2 and H7N7 and new subtypes viruses H5N6 and H7N9). The results showed that all the three humanized mAbs (F10, H98 and H40) displayed different degrees of virus neutralization activities when encountered with different subtypes of influenza viruses. Remarkably, the humanized monoclonal antibody F10 produced higher and broader neutralization titers (range 25–1.56 μg/ml) than those of the other two humanized mAbs (H98 (range 50–3.12 μg/ml), H40 (range 50–5.56 μg/ml)) to against the viruses H5N1, H1N1, H3N2, H7N7, H5N6 and H7N9. This mAb may represent a new class of heterosubtypic neutralizing humanized mAb that could replace vaccines and chemical drugs.
- Published
- 2019
33. Lasting antibody and T cell responses to SARS-CoV-2 in COVID-19 patients three months after infection
- Author
-
Ji Yan Zhang, Qing Duan, Weiyang Sun, Qing Yang Wang, En Tao Li, Sheng Xiang Ji, Yan Li, Yu Wei Gao, Xiao Li Zhang, Fei Hu Yan, Xiao Wei, Xiao Lin Jiang, Guo Lin Wang, Xiang Na Zhao, Tie Cheng Wang, Yu Wen Zhang, Mai Juan Ma, Zeng Qiang Kou, Li Jun Duan, Lin Yao, Xue Feng Wang, Cun Bao Li, and Dian Min Kang
- Subjects
0301 basic medicine ,CD4-Positive T-Lymphocytes ,Male ,Epidemiology ,T-Lymphocytes ,General Physics and Astronomy ,CD8-Positive T-Lymphocytes ,Antibodies, Viral ,Immunoglobulin G ,0302 clinical medicine ,Medicine ,Interferon gamma ,Receptor ,Multidisciplinary ,biology ,Middle Aged ,medicine.anatomical_structure ,Phenotype ,Female ,Antibody ,medicine.drug ,Adult ,Receptors, CCR7 ,Science ,T cell ,General Biochemistry, Genetics and Molecular Biology ,Article ,Antibodies ,03 medical and health sciences ,Interferon-gamma ,Immunity ,Humans ,business.industry ,SARS-CoV-2 ,fungi ,COVID-19 ,General Chemistry ,Antimicrobial responses ,Antibodies, Neutralizing ,Kinetics ,030104 developmental biology ,Immunoglobulin M ,Viral infection ,Immunology ,biology.protein ,Leukocyte Common Antigens ,business ,Immunologic Memory ,030217 neurology & neurosurgery ,CD8 - Abstract
The dynamics, duration, and nature of immunity produced during SARS-CoV-2 infection are still unclear. Here, we longitudinally measured virus-neutralising antibody, specific antibodies against the spike (S) protein, receptor-binding domain (RBD), and the nucleoprotein (N) of SARS-CoV-2, as well as T cell responses, in 25 SARS-CoV-2-infected patients up to 121 days post-symptom onset (PSO). All patients seroconvert for IgG against N, S, or RBD, as well as IgM against RBD, and produce neutralising antibodies (NAb) by 14 days PSO, with the peak levels attained by 15–30 days PSO. Anti-SARS-CoV-2 IgG and NAb remain detectable and relatively stable 3–4 months PSO, whereas IgM antibody rapidly decay. Approximately 65% of patients have detectable SARS-CoV-2-specific CD4+ or CD8+ T cell responses 3–4 months PSO. Our results thus provide critical evidence that IgG, NAb, and T cell responses persist in the majority of patients for at least 3–4 months after infection., Understanding if lasting immune responses can be induced by SARS-CoV-2 infection is important for controlling the COVID-19 pandemic. Here, the authors show, in a cohort of 25 patients, that IgG and T cell responses, as well as neutralising antibody, are still detectable against various SARS-CoV-2 proteins 3 months post-symptom onset, while IgM levels largely wane at this time.
- Published
- 2021
34. The application of a safe neutralization assay for Ebolavirus using lentivirus-based pseudotyped virus
- Author
-
Hualei Wang, Weiyang Sun, Hongbin He, Hongli Jin, Shengnan Xu, Cui Jiao, Hong-Mei Wang, Zengguo Cao, Feng Na, Fangfang Wu, Tiecheng Wang, Gary Wong, Yongkun Zhao, Ying Zhang, Xianzhu Xia, Yang Songtao, Hang Chi, and Yuwei Gao
- Subjects
Ebolavirus ,biology ,Immunogenicity ,medicine.disease_cause ,biology.organism_classification ,Virology ,Virus ,Neutralization ,Sierra leone ,Titer ,Lentivirus ,biology.protein ,medicine ,Neutralizing antibody - Abstract
Ebolavirus (EBOV) is responsible for several EBOV disease (EVD) outbreaks in Africa, with a fatality rate of up to 90%. During 2014-2016, An epidemic of EVD spread throughout Sierra Leone, Guinea and Liberia, and killed over 11,000 people. EBOV began to circulate again in the Democratic Republic of Congo in 2018. Due to the need for a BSL-4 facility to manipulate this virus, the development and improvement of specific therapeutics has been hindered. As a result, it is imperative to perform reliable research on EBOV under lowered BSL restrictions. In this study, we developed a safe neutralization assay based on pseudotyped EBOV, which incorporates the glycoprotein of the 2014 EBOV epidemic strain into a lentivirus vector. Our results demonstrated that the tropism of pseudotyped EBOV was similar to that of authentic EBOV, but with only one infection cycle. And neutralizing activity of both authentic EBOV and pseudotyped EBOV were compared in neutralization assay using three different samples of antibody-based reagents against EBOV, similar results were obtained. In addition, an indirect ELISA was performed to show the relationship between IgG and neutralizing antibody against EBOV detected by our pseudotyped EBOV-based neutralization assay. As expected, the neutralizing antibody titers varied with the IgG titers detected by indirect ELISA, and a correlation between the results of the two assays was identified. By comparison with two different assays, the reliability of the results detected by the pseudotyped EBOV-based neutralization assay was confirmed. Collectively, in the absence of BSL-4 restrictions, pseudotyped EBOV production and neutralizing activity evaluation can be performed safely and in a manner that is neither labor- nor time-consuming, providing a simple and safe method for EBOV-neutralizing antibody detection and the assessment of immunogenicity of EBOV vaccines. All these remarkable advantages of the newly established assay highlight its potential to further application in assessment of immunogenicity of EBOV vaccine candidates.
- Published
- 2020
35. The Application of a Safe Neutralization Assay for Ebolavirus Using Lentivirus-Based Pseudotyped Virus
- Author
-
Tiecheng Wang, Yuwei Gao, Hongli Jin, Cuicui Jiao, Weiyang Sun, Zengguo Cao, Na Feng, Fangfang Wu, Yang Songtao, Hualei Wang, Yongkun Zhao, Ying Zhang, Xianzhu Xia, Hang Chi, and Gary Wong
- Subjects
Ebolavirus ,biology ,business.industry ,Immunogenicity ,biology.organism_classification ,medicine.disease_cause ,Virology ,Virus ,Neutralization ,Sierra leone ,Lentivirus ,Medicine ,Vector (molecular biology) ,business ,Tropism - Abstract
Background: Ebolavirus (EBOV) is responsible for several EBOV disease (EVD) outbreaks in Africa, with a fatality rate of up to 90%. During 2014-2016, An epidemic of EVD spread throughout Sierra Leone, Guinea and Liberia, and killed over 11,000 people. EBOV began to circulate again in the Democratic Republic of Congo in 2018. Due to the need for a BSL-4 facility to manipulate this virus, the development and improvement of specific therapeutics has been hindered. As a result, it is imperative to perform reliable research on EBOV under lowered BSL restrictions. Methods: Based on lentivirus vector, we developed a safe EBOV pseudotyped virus, which was used into a neutralization assay. The tropism and neutralizing activity of both authentic EBOV and EBOV pseudotyped virus were compared, using three different samples of antibody-based agents against EBOV. Findings: Our results demonstrated that the tropism of EBOV pseudotyped virus was similar to that of authentic EBOV, but with only one infection cycle. After utilizing to neutralization assay in the absence of BSL-4 restrictions, the EBOV pseudotyped virus-based assay showed similar results with the live EBOV neutralization assay and indirect ELISA. Interpretation: The remarkable simplicity and safety of EBOV pseudotyped virus-based neutralization assay highlight its potential to further application in assessment of immunogenicity of EBOV vaccine candidates. Funding: This work was supported by the National Science and Technology Major Projectof the Ministry of Science and Technology of China (grants 2015ZX09102025). Declaration of Interest: The authors have no conflicts of interest to declare. Ethical Approval: All animal studies in this work were approved bythe Animal Care and Use Committee of Chinese People’s Liberation Army (No. SYXK2009-045). All efforts were made to minimize animal suffering.
- Published
- 2020
36. Additional file 1 of Antibiotic resistance in patients with clinical features of healthcare-associated infections in an urban tertiary hospital in Sierra Leone: a cross-sectional study
- Author
-
Lakoh, Sulaiman, Letian Li, Sevalie, Stephen, Xuejun Guo, Olukemi Adekanmbi, Yang, Guang, Oladimeji Adebayo, Yi, Le, Coker, Joshua, Shuchao Wang, Tiecheng Wang, Weiyang Sun, Abdulrazaq Habib, and Klein, Eili
- Subjects
animal structures ,virus diseases - Abstract
Additional file 1. Antibiotic use among adult patients with clinical features of HAI.
- Published
- 2020
- Full Text
- View/download PDF
37. Inclusion of membrane-anchored LTB or flagellin protein in H5N1 virus-like particles enhances protective responses following intramuscular and oral immunization of mice
- Author
-
Lingnan Meng, Jing Liu, Yuanguo Li, Zhengyan Yang, Yongkun Zhao, Kun Zhang, Zhijun Yu, Zhiguang Ren, Xianliang Ji, Na Feng, Yuwei Gao, Hualei Wang, Wang Zhizeng, Xianzhu Xia, Songtao Yang, Weiyang Sun, Tiecheng Wang, and Xiaoyu Sang
- Subjects
0301 basic medicine ,viruses ,Bacterial Toxins ,030106 microbiology ,Administration, Oral ,Neuraminidase ,Heterologous ,Hemagglutinin Glycoproteins, Influenza Virus ,Enterotoxin ,Injections, Intramuscular ,complex mixtures ,Viral Matrix Proteins ,Enterotoxins ,Mice ,03 medical and health sciences ,Immunogenicity, Vaccine ,Immune system ,Orthomyxoviridae Infections ,Antigen ,Animals ,Vaccines, Virus-Like Particle ,Mice, Inbred BALB C ,Influenza A Virus, H5N1 Subtype ,General Veterinary ,General Immunology and Microbiology ,biology ,Escherichia coli Proteins ,Immunogenicity ,Public Health, Environmental and Occupational Health ,virus diseases ,biochemical phenomena, metabolism, and nutrition ,Virology ,030104 developmental biology ,Infectious Diseases ,Immunization ,Influenza Vaccines ,biology.protein ,bacteria ,Molecular Medicine ,Female ,Flagellin - Abstract
We previously demonstrated that intramuscular immunization with virus-like particles (VLPs) composed of the haemagglutinin (HA), neuraminidase (NA), and matrix (M1) proteins of A/meerkat/Shanghai/SH-1/2012 (clade 2.3.2.1) protected mice from lethal challenge with viruses from other H5 HPAI clades. The inclusion of additional proteins that can serve as immunological adjuvants in VLPs may enhance adaptive immune responses following vaccination, and oral vaccines may represent the safest choice. Here, we report the generation of H5N1 VLPs composed of the viral HA, NA, and M1 proteins and membrane-anchored forms of the Escherichia coli heat-labile enterotoxin B subunit protein (LTB) or the Toll-like receptor 5 ligand flagellin (Flic). Mice intramuscularly or orally immunized with VLPs containing LTB or Flic generated greater humoural and cellular immune responses than those administered H5N1 VLPs without LTB or Flic. Intramuscular immunization with VLPs protected mice from lethal challenge with homologous or heterologous H5N1 viruses irrespective of whether the VLPs additionally included LTB or Flic. In contrast, oral immunization of mice with LTB- or Flic-VLPs conferred substantial protection against lethal challenge with both homologous and heterologous H5N1 influenza viruses, whereas mice immunized orally with VLPs lacking LTB and Flic universally succumbed to infection. Mice immunized orally with LTB- or Flic-VLPs showed 10-fold higher virus-specific IgG titres than mice immunized with H5N1-VLPs lacking LTB or Flic. Collectively, these results indicate that the inclusion of immunostimulatory proteins, such as LTB and Flic, in VLP-based vaccines may represent a promising new approach for the control of current H5N1 HPAI outbreaks by eliciting higher humoural and cellular immune responses and conferring improved cross-clade protection.
- Published
- 2018
38. Intramuscular and intranasal immunization with an H7N9 influenza virus-like particle vaccine protects mice against lethal influenza virus challenge
- Author
-
Na Feng, Tiecheng Wang, Jing Liu, Yuanguo Li, Weiyang Sun, Kun Zhang, Zhengyan Yang, Yuanfang Ma, Zhiguang Ren, Songtao Yang, Zhijun Yu, Xiaoyu Sang, Xianzhu Xia, Yuwei Gao, Xianliang Ji, Lingnan Meng, Hualei Wang, and Yongkun Zhao
- Subjects
0301 basic medicine ,viruses ,Immunology ,Neuraminidase ,Hemagglutinin (influenza) ,Hemagglutinin Glycoproteins, Influenza Virus ,Antibodies, Viral ,Influenza A Virus, H7N9 Subtype ,Injections, Intramuscular ,Virus ,Viral Matrix Proteins ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Orthomyxoviridae Infections ,Virus-like particle ,Influenza, Human ,Animals ,Humans ,Immunology and Allergy ,Medicine ,030212 general & internal medicine ,Administration, Intranasal ,Pharmacology ,Immunity, Cellular ,Mice, Inbred BALB C ,biology ,business.industry ,Immunogenicity ,Virion ,biochemical phenomena, metabolism, and nutrition ,Virology ,030104 developmental biology ,Immunization ,Influenza Vaccines ,biology.protein ,Female ,Nasal administration ,business - Abstract
The H7N9 influenza virus epidemic has been associated with a high mortality rate in China. Therefore, to prevent the H7N9 virus from causing further damage, developing a safe and effective vaccine is necessary. In this study, a vaccine candidate consisting of virus-like particles (VLPs) based on H7N9 A/Shanghai/2/2013 and containing hemagglutinin (HA), neuraminidase (NA), and matrix protein (M1) was successfully produced using a baculovirus (BV) expression system. Immunization experiments showed that strong humoral and cellular immune responses could be induced by the developed VLPs when administered via either the intramuscular (IM) or intranasal (IN) immunization routes. Notably, VLPs administered via both immunization routes provided 100% protection against lethal infection caused by the H7N9 virus. The IN immunization with 40μg of H7N9 VLPs induced strong lung IgA and lung tissue resident memory (TRM) cell-mediated local immune responses. These results provide evidence for the development of an effective preventive vaccine against the H7N9 virus based on VLPs administered through both the IM and IN immunization routes.
- Published
- 2018
39. Characterization of Canine Influenza Virus A (H3N2) Circulating in Dogs in China from 2016 to 2018
- Author
-
Li Yuanguo, Qing Xia, Weiyang Sun, Hongyu Sun, Zhou Bo, Xianzhu Xia, Yuxiu Liu, Yunyi Kong, Xinghai Zhang, Jin Ningyi, Entao Li, Ye Feng, Ye Ge, Xinyu Hu, Haiyang Xiang, Hongbin He, Tiecheng Wang, Chaoxiang Lv, Xuefeng Wang, Meng Keyin, Yuwei Gao, and Shushan Fang
- Subjects
China ,viruses ,serological surveillance ,Canine influenza ,Guinea Pigs ,Prevalence ,Biology ,Microbiology ,Airborne transmission ,Article ,Virus ,Serology ,Mice ,Dogs ,Orthomyxoviridae Infections ,Virology ,evolution ,medicine ,Animals ,Dog Diseases ,canine influenza virus ,Phylogeny ,Mice, Inbred BALB C ,Transmission (medicine) ,Influenza A Virus, H3N2 Subtype ,Strain (biology) ,transmission ,virus diseases ,Respiratory Aerosols and Droplets ,QR1-502 ,Ducks ,Infectious Diseases ,medicine.anatomical_structure ,Female ,Chickens ,Respiratory tract - Abstract
Avian H3N2 influenza virus follows cross-host transmission and has spread among dogs in Asia since 2005. After 2015–2016, a new H3N2 subtype canine influenza epidemic occurred in dogs in North America and Asia. The disease prevalence was assessed by virological and serological surveillance in dogs in China. Herein, five H3N2 canine influenza virus (CIV) strains were isolated from 1185 Chinese canine respiratory disease samples in 2017–2018, these strains were on the evolutionary branch of the North American CIVs after 2016 and genetically far from the classical canine H3N2 strain discovered in China before 2016. Serological surveillance showed an HI antibody positive rate of 6.68%. H3N2 was prevalent in the coastal areas and northeastern regions of China. In 2018, it became the primary epidemic strain in the country. The QK01 strain of H3N2 showed high efficiency in transmission among dogs through respiratory droplets. Nevertheless, the virus only replicated in the upper respiratory tract and exhibited low pathogenicity in mice. Furthermore, highly efficient transmission by direct contact other than respiratory droplet transmission was found in a guinea pig model. The low-level replication in avian species other than ducks could not facilitate contact and airborne transmission in chickens. The current results indicated that a novel H3N2 virus has become a predominant epidemic strain in dogs in China since 2016 and acquired highly efficient transmissibility but could not be replicated in avian species. Thus, further monitoring is required for designing optimal immunoprophylactic tools for dogs and estimating the zoonotic risk of CIV in China.
- Published
- 2021
40. Rapid acquisition adaptive amino acid substitutions involved in the virulence enhancement of an H1N2 avian influenza virus in mice
- Author
-
Xinghai Zhang, Weiyang Sun, Chuqi Zhao, Zhijun Yu, Yuwei Gao, Xianzhu Xia, and Kaihui Cheng
- Subjects
0301 basic medicine ,Genes, Viral ,Sequence analysis ,animal diseases ,030106 microbiology ,Adaptation, Biological ,Virulence ,Biology ,Virus Replication ,Microbiology ,Virus ,Cell Line ,Birds ,Mice ,Viral Proteins ,03 medical and health sciences ,Dogs ,Orthomyxoviridae Infections ,In vivo ,Influenza A Virus, H1N2 Subtype ,Animals ,Phylogeny ,Ovum ,chemistry.chemical_classification ,General Veterinary ,virus diseases ,General Medicine ,Virology ,In vitro ,Amino acid ,030104 developmental biology ,Amino Acid Substitution ,chemistry ,Influenza in Birds ,Tissue tropism ,Adaptation ,Chickens - Abstract
Although H1N2 avian influenza virus (AIV) only infect birds, documented cases of swine infection with H1N2 influenza viruses suggest this subtype AIV may pose a potential threat to mammals. Here, we generated mouse-adapted variants of a H1N2 AIV to identify adaptive changes that increased virulence in mammals. MLD50 of the variants were reduced >1000-fold compared to the parental virus. Variants displayed enhanced replication in vitro and in vivo, and replicate in extrapulmonary organs. These data show that enhanced replication capacity and expanded tissue tropism may increase the virulence of H1N2 AIV in mice. Sequence analysis revealed multiple amino acid substitutions in the PB2 (L134H, I647L, and D701N), HA (G228S), and M1 (D231N) proteins. These results indicate that H1N2 AIV can rapidly acquire adaptive amino acid substitutions in mammalian hosts, and these amino acid substitutions collaboratively enhance the ability of H1N2 AIV to replicate and cause severe disease in mammals.
- Published
- 2017
41. The innate immunity of guinea pigs against highly pathogenic avian influenza virus infection
- Author
-
Tiecheng Wang, Zhaowei Zhang, Yuanguo Li, Zhiguang Ren, Yuwei Gao, Weiyang Sun, Na Feng, Xuemei Zhang, Wenjun Liu, Xianzhu Xia, Lijuan Sun, Xiaoyu Sang, Jing Li, Ming Liao, Yongkun Zhao, Zhijun Yu, Songtao Yang, Hualei Wang, Peter R. Wilker, Kun Zhang, Hualan Chen, Jing Liu, Weiwei Xu, and Peirong Jiao
- Subjects
0301 basic medicine ,Influenza vaccine ,viruses ,Guinea Pigs ,Virus Replication ,medicine.disease_cause ,Virus ,Cell Line ,RIG-I ,Guinea pig ,03 medical and health sciences ,Orthomyxoviridae Infections ,medicine ,Animals ,Lung ,innate immunity ,Influenza A Virus, H5N1 Subtype ,030102 biochemistry & molecular biology ,business.industry ,Gene Expression Profiling ,GBP-1 ,highly pathogenic avian influenza virus ,Zoonosis ,virus diseases ,Complement System Proteins ,Genomics ,Viral Load ,Biological product ,medicine.disease ,Virology ,Immunity, Innate ,Influenza A virus subtype H5N1 ,Disease Models, Animal ,030104 developmental biology ,Gene Expression Regulation ,Oncology ,Viral replication ,Host-Pathogen Interactions ,Female ,business ,Biomarkers ,guinea pig ,Research Paper - Abstract
// Kun Zhang 1, 2 , Wei wei Xu 1 , Zhaowei Zhang 1 , Jing liu 1 , Jing Li 3 , Lijuan Sun 4 , Weiyang Sun 1 , Peirong Jiao 5 , Xiaoyu Sang 1 , Zhiguang Ren 1 , Zhijun Yu 1 , Yuanguo Li 1 , Na Feng 1 , Tiecheng Wang 1 , Hualei Wang 1 , Songtao Yang 1 , Yongkun Zhao 1 , Xuemei Zhang 4 , Peter R. Wilker 6 , WenJun Liu 3 , Ming Liao 5 , Hualan Chen 7 , Yuwei Gao 1 , Xianzhu Xia 1 1 Key Laboratory of Jilin Province for Zoonosis Prevention and Control, The Military Veterinary Institute, Academy of Military Medical Science of PLA, Changchun, 130122, PR China 2 Philips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth University, Richmond, Virginia, 23298, USA 3 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, PR China 4 Department of Influenza Vaccine, Changchun Institute of Biological Product, Changchun, 130062, PR China 5 College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, PR China 6 Department of Microbiology, University of Wisconsin La Crosse, La Crosse, Wisconsin, 54601, USA 7 State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, PR China Correspondence to: Yuwei Gao, email: gaoyuwei@gmail.com Xianzhu Xia, email: xiaxzh@cae.cn Keywords: innate immunity, guinea pig, highly pathogenic avian influenza virus, GBP-1, RIG-I Received: August 26, 2016 Accepted: February 27, 2017 Published: March 23, 2017 ABSTRACT H5N1 avian influenza viruses are a major pandemic concern. In contrast to the highly virulent phenotype of H5N1 in humans and many animal models, guinea pigs do not typically display signs of severe disease in response to H5N1 virus infection. Here, proteomic and transcriptional profiling were applied to identify host factors that account for the observed attenuation of A/Tiger/Harbin/01/2002 (H5N1) virulence in guinea pigs. RIG-I and numerous interferon stimulated genes were among host proteins with altered expression in guinea pig lungs during H5N1 infection. Overexpression of RIG-I or the RIG-I adaptor protein MAVS in guinea pig cell lines inhibited H5N1 replication. Endogenous GBP-1 expression was required for RIG-I mediated inhibition of viral replication upstream of the activity of MAVS. Furthermore, we show that guinea pig complement is involved in viral clearance, the regulation of inflammation, and cellular apoptosis during influenza virus infection of guinea pigs. This work uncovers features of the guinea pig innate immune response to influenza that may render guinea pigs resistant to highly pathogenic influenza viruses.
- Published
- 2017
42. Autophagy is highly targeted among host comparative proteomes during infection with different virulent RABV strains
- Author
-
Pengfei Hou, Xuexing Zheng, Hang Chi, Hongli Jin, Weiyang Sun, Na Feng, Cuicui Jiao, Lina Wang, Nan Li, Guixue Hu, Xianzhu Xia, Ling Li, Hualei Wang, Yongkun Zhao, Yuwei Gao, Qian Li, Jianzhong Wang, Tiecheng Wang, Zengguo Cao, Changchun Tu, Pei Huang, and Songtao Yang
- Subjects
0301 basic medicine ,Proteomics ,autophagy ,Proteome ,Rabies ,differential virulence ,Blotting, Western ,Virulence ,medicine.disease_cause ,Virus ,03 medical and health sciences ,Mice ,Microscopy, Electron, Transmission ,Medicine ,Animals ,Neurotropic virus ,Mice, Inbred BALB C ,business.industry ,Autophagy ,Rabies virus ,Zoonosis ,proteomics analysis ,medicine.disease ,Virology ,Disease Models, Animal ,030104 developmental biology ,Oncology ,Infectious disease (medical specialty) ,Female ,business ,Research Paper - Abstract
// Ling Li 1, 2 , Hongli Jin 1, 2 , Hualei Wang 2, 4 , Zengguo Cao 2 , Na Feng 2, 4 , Jianzhong Wang 3 , Yongkun Zhao 2 , Xuexing Zheng 2, 5 , Pengfei Hou 1, 2 , Nan Li 2 , Hang Chi 2 , Pei Huang 2, 3 , Cuicui Jiao 2 , Qian Li 2 , Lina Wang 2, 3 , Tiecheng Wang 2 , Weiyang Sun 2 , Yuwei Gao 2, 4 , Changchun Tu 2 , Guixue Hu 3 , Songtao Yang 2, 4 , Xianzhu Xia 2, 4 1 Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, China 2 Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, China 3 Department of Preventive Veterinary Medicine, College of Animal Science and Technology, Jilin Agricultural University, Changchun, China 4 Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou, China 5 School of Public Health, Shandong University, Jinan, China Correspondence to: Hualei Wang email: whl831125@163.com Songtao Yang email: yst62041@163.com Guixue Hu email: huguixue901103@163.com Keywords: rabies virus, proteome, proteomics analysis, autophagy, differential virulence Received: May 23, 2016 Accepted: January 16, 2017 Published: February 08, 2017 ABSTRACT Rabies virus (RABV) is a neurotropic virus that causes serious disease in humans and animals worldwide. It has been reported that different RABV strains can result in divergent prognoses in animal model. To identify host factors that affect different infection processes, a kinetic analysis of host proteome alterations in mouse brains infected with different virulent RABV strains was performed using isobaric tags for a relative and absolute quantification (iTRAQ)-liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomics approach, and this analysis identified 147 differentially expressed proteins (DEPs) between the pathogenic challenge virus standard (CVS)-11 strain and the attenuated SRV9 strain. Bioinformatics analyses of these DEPs revealed that autophagy and several pathways associated with autophagy, such as mammalian target of rapamycin (mTOR) signaling, p70S6K signaling, nuclear factor erythroid 2-related factor 2 (NRF2)-mediated oxidative stress and superoxide radical degradation, were dysregulated. Validation of the proteomic data showed that attenuated SRV9 induced more autophagosome accumulation than CVS-11 in an in vitro model. Our findings provide new insights into the pathogenesis of RABV and encourage further studies on this topic.
- Published
- 2017
43. Passive immunotherapy for Middle East Respiratory Syndrome coronavirus infection with equine immunoglobulin or immunoglobulin fragments in a mouse model
- Author
-
Yongkun Zhao, Tiecheng Wang, Hualei Wang, Ling Chen, Songtao Yang, Nanshan Zhong, Stanley Perlman, Xianzhu Xia, Weiwei Gai, Xuexing Zheng, Jincun Zhao, Hongli Jin, Jinghua Yan, Yuwei Gao, Feihu Yan, Qian Wang, Chufang Li, Weiyang Sun, Boning Qiu, and Chong Wang
- Subjects
0301 basic medicine ,Middle East respiratory syndrome coronavirus ,viruses ,Antibodies, Viral ,medicine.disease_cause ,Article ,Virus ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Equine immune serum ,Virology ,Immunoglobulin ,medicine ,Animals ,Humans ,Animal model ,Horses ,Receptors, Immunologic ,F(ab’)2 fragment ,Immunoglobulin Fragments ,Respiratory Tract Infections ,Coronavirus ,Pharmacology ,biology ,Immunization, Passive ,virus diseases ,respiratory system ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,Antibodies, Neutralizing ,respiratory tract diseases ,Disease Models, Animal ,Titer ,030104 developmental biology ,Immunoglobulin G ,030220 oncology & carcinogenesis ,Middle East Respiratory Syndrome Coronavirus ,biology.protein ,Middle East respiratory syndrome ,Antibody ,Coronavirus Infections - Abstract
Middle East Respiratory Syndrome (MERS) is a highly lethal pulmonary infection caused by a coronavirus (CoV), MERS-CoV. With the continuing spread of MERS-CoV, prophylactic and therapeutic treatments are urgently needed. In this study, we prepared purified equine F(ab’)2 from horses immunized with MERS-CoV virus-like particles (VLPs) expressing MERS-CoV S, M and E proteins. Both IgG and F(ab’)2 efficiently neutralized MERS-CoV replication in tissue culture. Passive transfer of equine immune antibodies significantly reduced virus titers and accelerated virus clearance from the lungs of MERS-CoV infected mice. Our data show that horses immunized with MERS-CoV VLPs can serve as a primary source of protective F(ab’)2 for potential use in the prophylactic or therapeutic treatment of exposed or infected patients., Highlights • Healthy horses immunized with MERS-CoV virus-like particles rapidly generate high titers of virus neutralizing antibodies. • Passive transfer of equine immune antibodies significantly reduced virus titers from the lungs of MERS-CoV infected mice. • F(ab’)2 fragments prepared by digestion of antibody with pepsin to reduce possible allergic responses. • Equine immune antibodies are polyclonal and recognize more antigen determinants in MERS-CoV spike protein.
- Published
- 2017
44. Concealment of time delay signature of chaotic output in a slave semiconductor laser with chaos laser injection
- Author
-
Xiaoxu Zhang, Tianan Wu, Weiyang Sun, and Shenghai Zhang
- Subjects
Physics ,business.industry ,Bandwidth (signal processing) ,Autocorrelation ,Chaotic ,Phase (waves) ,02 engineering and technology ,Mutual information ,Laser ,Atomic and Molecular Physics, and Optics ,Signature (logic) ,Electronic, Optical and Magnetic Materials ,law.invention ,Semiconductor laser theory ,020210 optoelectronics & photonics ,Optics ,law ,0202 electrical engineering, electronic engineering, information engineering ,Electrical and Electronic Engineering ,Physical and Theoretical Chemistry ,business - Abstract
An improved chaotic laser system, which has a slave semiconductor laser (SL) injected by a master SL with double optical feedback (DOF), is proposed, so that the time delay (TD) signature can be successfully concealed from both intensity and phase chaos via choosing appropriate parameters. The TD signature is investigated by employing autocorrelation function (ACF) and mutual information (MI) function. Through analyzing the influence on TD signature in the region of injection current and injection strength for the slave SL, we find that, for both intensity chaos and phase chaos, the TD signature can be easily concealed under weak injection strength. When the injection strength is strong, we can not only successfully conceal TD signature, but also improve the bandwidth of chaotic laser output by choosing the optimal detuning frequency.
- Published
- 2016
45. Genetically Modified Rabies Virus Vector-Based Rift Valley Fever Virus Vaccine is Safe and Induces Efficacious Immune Responses in Mice
- Author
-
Hang Chi, Shengnan Zhang, Tiecheng Wang, Yongkun Zhao, Xianzhu Xia, Weiyang Sun, Gary Wong, Na Feng, Hongli Jin, Qiuxue Han, Yuwei Gao, Feihu Yan, Hualei Wang, Jun Wu, Bo Liu, Yuhai Bi, Jianzhong Wang, Meng Hao, and Songtao Yang
- Subjects
0301 basic medicine ,Cellular immunity ,Rift Valley Fever ,T-Lymphocytes ,030106 microbiology ,Population ,RVFV-specific IgG antibodies ,lcsh:QR1-502 ,Biology ,medicine.disease_cause ,Antibodies, Viral ,Virus Replication ,lcsh:Microbiology ,Article ,03 medical and health sciences ,Mice ,Immune system ,Adjuvants, Immunologic ,Virology ,parasitic diseases ,medicine ,Animals ,Rift Valley fever ,education ,Inactivated vaccine ,Adjuvant ,education.field_of_study ,Mice, Inbred BALB C ,Vaccines, Synthetic ,Rabies virus ,Vaccination ,Viral Vaccines ,medicine.disease ,Rift Valley fever virus ,Antibodies, Neutralizing ,Immunity, Humoral ,Disease Models, Animal ,030104 developmental biology ,Infectious Diseases ,Immunization ,Rabies Vaccines ,Vaccines, Inactivated ,Immunoglobulin G ,Rabies ,Female - Abstract
Rift Valley fever virus (RVFV), which causes Rift Valley fever (RVF), is a mosquito-borne zoonotic pathogen that causes serious morbidity and mortality in livestock and humans. RVF is a World Health Organization (WHO) priority disease and, together with rabies, is a major health burden in Africa. Here, we present the development and characterization of an inactivated recombinant RVFV and rabies virus (RABV) vaccine candidate (rSRV9-eGn). Immunization with rSRV9-eGn stimulated the production of RVFV-specific IgG antibodies and induced humoral and cellular immunity in mice but did not induce the production of neutralizing antibodies. IgG1 and IgG2a were the main isotypes observed by IgG subtype detection, and IgG3 antibodies were not detected. The ratios of IgG1/IgG2a >, 1 indicated a Type 2 humoral immune response. An effective vaccine is intended to establish a long-lived population of memory T cells, and mice generated memory cells among the proliferating T cell population after immunization with rSRV9-eGn, with effector memory T cells (TEM) as the major population. Due to the lack of prophylactic treatment experiments, it is impossible to predict whether this vaccine can protect animals from RVFV infection with only high titres of anti-RVFV IgG antibodies and no neutralizing antibodies induced, and thus, protection confirmation needs further verification. However, this RVFV vaccine designed with RABV as the vector provides ideas for the development of vaccines that prevent RVFV and RABV infections.
- Published
- 2019
- Full Text
- View/download PDF
46. A Novel Bacterium-Like Particle Vaccine Displaying the MERS-CoV Receptor-Binding Domain Induces Specific Mucosal and Systemic Immune Responses in Mice
- Author
-
Shengnan Zhang, Yongkun Zhao, Songtao Yang, Hongli Jin, Weiyang Sun, Tiecheng Wang, Jianzhong Wang, Xianzhu Xia, Feihu Yan, Ying Zhang, Hualei Wang, Hang Chi, Pei Huang, Zhenshan Wang, Ruo Mo, Yuwei Gao, Yuhai Bi, Guohua Li, Entao Li, Na Feng, and Chuanyu Liu
- Subjects
0301 basic medicine ,Middle East respiratory syndrome coronavirus ,medicine.medical_treatment ,Recombinant Fusion Proteins ,030106 microbiology ,Lysin ,lcsh:QR1-502 ,medicine.disease_cause ,Antibodies, Viral ,lcsh:Microbiology ,Article ,intranasal administration ,03 medical and health sciences ,Mice ,MERS-CoV ,Immune system ,Adjuvants, Immunologic ,Virology ,medicine ,Animals ,Protein Interaction Domains and Motifs ,Intestinal Mucosa ,Administration, Intranasal ,Coronavirus ,biology ,bacterium-like particles ,Lactococcus lactis ,Immunity ,Viral Vaccines ,biology.organism_classification ,Fusion protein ,Antibodies, Neutralizing ,Immunoglobulin A ,030104 developmental biology ,Infectious Diseases ,mucosal immune ,Spike Glycoprotein, Coronavirus ,Vaccines, Subunit ,Middle East Respiratory Syndrome Coronavirus ,Nasal administration ,Immunization ,subunit vaccine ,Coronavirus Infections ,Adjuvant ,Spleen - Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV), a new coronavirus that has been causing severe and fatal acute respiratory illnesses in humans since its outbreak in 2012, has raised public fear worldwide. The development of prophylactics and therapeutics is urgently needed to prevent and control MERS-CoV infections. In this study, a bacterium (Lactococcus lactis)-like particle (BLP) vaccine displaying the MERS-CoV receptor-binding domain (RBD) was developed, and gram-positive enhancer matrix (GEM) particles were used as substrates to externally bind to the MERS-CoV RBD through a protein anchor (PA). The designs included different numbers of lysin motif (LysM) repeats in the PAs linked by linkers (RBD-linker-PA2 (RLP2), RBD-linker-PA3 (RLP3) and RBD-PA3 (RP3)), and three LysM repeats and a linker in the fusion proteins increased the binding activity to the RBD. The specific immune responses were tested by intranasally immunizing mice with RLP3-GEM with or without the adjuvant GEL01. The results showed that GEL01-adjuvanted RLP3-GEM increased the systemic humoral, cellular and local mucosal immune responses in the mouse model, especially in the intestinal tract. The above results indicate that the MERS-CoV BLP product has the potential to be developed into a promising mucosal candidate vaccine to protect against MERS-CoV infections.
- Published
- 2019
- Full Text
- View/download PDF
47. Antibiotic resistance in patients with clinical features of healthcare-associated infections in an urban tertiary hospital in Sierra Leone: a cross-sectional study
- Author
-
Le Yi, Abdulrazaq G. Habib, Joshua Coker, Weiyang Sun, Shuchao Wang, Tiecheng Wang, Eili Y. Klein, Guang Yang, Oladimeji Adebayo, Stephen Sevalie, Xuejun Guo, Sulaiman Lakoh, Olukemi Adekanmbi, and Letian Li
- Subjects
0301 basic medicine ,Microbiology (medical) ,Adult ,Male ,medicine.medical_specialty ,Cross-sectional study ,030106 microbiology ,Prevalence ,Drug Resistance ,Drug resistance ,Comorbidity ,Microbial Sensitivity Tests ,Urine ,lcsh:Infectious and parasitic diseases ,Sierra leone ,Sierra Leone ,Tertiary Care Centers ,03 medical and health sciences ,0302 clinical medicine ,Medical microbiology ,Antibiotic resistance ,Internal medicine ,medicine ,Humans ,lcsh:RC109-216 ,Pharmacology (medical) ,030212 general & internal medicine ,Aged ,Cross Infection ,biology ,Bacteria ,business.industry ,Research ,Public Health, Environmental and Occupational Health ,Age Factors ,Sputum ,Urban Health ,Middle Aged ,biology.organism_classification ,Antibiotic resistance/stewardship/ bacteria/ diagnostic infrastructure ,Acinetobacter baumannii ,Anti-Bacterial Agents ,Infectious Diseases ,Cross-Sectional Studies ,Female ,medicine.symptom ,business - Abstract
Background Available data on antibiotic resistance in sub-Saharan Africa is limited despite its increasing threat to global public health. As there is no previous study on antibiotic resistance in patients with clinical features of healthcare-associated infections (HAIs) in Sierra Leone, research is needed to inform public health policies. Our study aimed to assess antibiotic resistance rates from isolates in the urine and sputum samples of patients with clinical features of HAIs. Methodology We conducted a cross-sectional study of adult inpatients aged ≥18 years at Connaught Hospital, an urban tertiary care hospital in Freetown between February and June 2018. Results Over the course of the study, we enrolled 164 patients. Risk factors for HAIs were previous antibiotic use (93.3%), comorbidities (58.5%) and age (≥65 years) (23.9%). Of the 164 samples, 89.6% were urine. Bacterial growth was recorded in 58.8% of cultured specimens; the type of specimen was an independent predictor of bacterial growth (p Escherichia coli and Klebsiella pneumoniae; 29.2% and 19.0% in urine samples and 18.8% and 31.3% in sputum samples, respectively. The overall resistance rates were 58% for all extended-spectrum beta-lactamase (ESBL)-producing organisms, 13.4% for carbapenem-resistant non-lactose fermenting gram-negative bacilli, 8.7% for carbapenem-resistant Acinetobacter baumannii (CRAB) and 1.3% for carbapenem-resistant Enterobacteriaceae (CRE). There were no carbapenem-resistant P. aeruginosa (CRPA) isolates but all Staphylococcus aureus isolates were methicillin-resistant S. aureus. Conclusion We demonstrated a high prevalence rate of ESBL-producing organisms which are a significant burden at the main tertiary hospital in Sierra Leone. Urgent action is needed to strengthen microbiological diagnostic infrastructure, initiate surveillance on antibiotic resistance and develop and implement policy framework on antibiotic stewardship.
- Published
- 2019
48. PB2 and hemagglutinin mutations confer a virulent phenotype on an H1N2 avian influenza virus in mice
- Author
-
Zhiguang Ren, Zhijun Yu, Weiyang Sun, Xianzhu Xia, Kaihui Cheng, Hongbin He, Xinghai Zhang, Yuwei Gao, Jiaqiang Wu, and Yongkun Zhao
- Subjects
viruses ,Adaptation, Biological ,Virulence ,Hemagglutinin (influenza) ,Hemagglutinin Glycoproteins, Influenza Virus ,Biology ,medicine.disease_cause ,Virus Replication ,Virus ,Cell Line ,Madin Darby Canine Kidney Cells ,Birds ,03 medical and health sciences ,Mice ,Viral Proteins ,Dogs ,Orthomyxoviridae Infections ,Virology ,Influenza A Virus, H1N2 Subtype ,Influenza A virus ,medicine ,Animals ,030304 developmental biology ,Mammals ,0303 health sciences ,Mutation ,Mice, Inbred BALB C ,030306 microbiology ,virus diseases ,General Medicine ,biochemical phenomena, metabolism, and nutrition ,Phenotype ,Influenza A virus subtype H5N1 ,respiratory tract diseases ,Amino Acid Substitution ,Influenza in Birds ,Tissue tropism ,biology.protein ,Female - Abstract
We previously obtained mouse-adapted variants of H1N2 avian influenza virus that contained PB2-L134H, PB2-I647L, PB2-D701N, HA-G228S, and M1-D231N mutations. Here, we analyzed the effects of these mutations on viral pathogenicity in a mammalian model. By evaluating the virulence of mouse-adapted H1N2 variants at different generations, we found that the PB2-D701N and HA-G228S mutations both contribute to the virulence of this virus in mammals. Furthermore, we found that the PB2-D701N and HA-G228S mutations both enhance the ability of the virus to replicate in vivo and in vitro and that the PB2-D701N substitution results in an expansion of viral tissue tropism. These results suggest that the PB2-D701N mutation and the HA-G228S mutation are the major mammalian determinants of H1N2 virus. These results help us to understand more about the mechanisms by which influenza viruses adapt to mammals, and monitoring of these mutations can be used in continuous influenza surveillance to assess the pandemic potential of avian influenza virus variants.
- Published
- 2019
49. A highly efficient recombinant canarypox virus-based vaccine against canine distemper virus constructed using the CRISPR/Cas9 gene editing method
- Author
-
Yuchen Gong, Ling Zhang, Weiyang Sun, Hongmei Wang, Li Wen, Xianyong Meng, Dong Haiman, Yuwei Gao, Songtao Yang, Yongkun Zhao, Hongbin He, Xianzhu Xia, Tiecheng Wang, Na Feng, Xiaofei Song, Chen Tingwei, and Jianzhong Wang
- Subjects
Male ,animal diseases ,viruses ,Foxes ,Hemagglutinins, Viral ,Hemagglutinin (influenza) ,Chick Embryo ,Canarypox virus ,Antibodies, Viral ,Microbiology ,Virus ,law.invention ,03 medical and health sciences ,Dogs ,law ,Chlorocebus aethiops ,medicine ,Animals ,CRISPR ,Distemper ,Seroconversion ,Distemper Virus, Canine ,Vero Cells ,Glycoproteins ,030304 developmental biology ,Gene Editing ,Vaccines, Synthetic ,0303 health sciences ,General Veterinary ,biology ,030306 microbiology ,Canine distemper ,virus diseases ,Viral Vaccines ,General Medicine ,Fibroblasts ,medicine.disease ,Virology ,Vaccination ,Mink ,biology.protein ,Recombinant DNA ,Female ,CRISPR-Cas Systems ,Chickens ,Viral Fusion Proteins - Abstract
Canine distemper virus (CDV) is the causative agent of canine distemper (CD), which is one of the most important infectious diseases affecting wild and domestic carnivores. Vaccination represents an effective approach to prevent CDV infection among domestic carnivores. Canarypox-vectored recombinant CD vaccines (such as Recombitek CDV, PureVax Ferret Distemper, and Merial) with the CDV hemagglutinin (H) and fusion (F) genes can induce a potent immune response in dogs and ferrets. However, the vaccine's effectiveness varies with the species. In the current study, we developed a highly efficient recombinant canarypox virus termed as "ALVAC-CDV-M-F-H/C5-" that contained CDV virus-like particles (VLPs) by using the CRISPR/Cas9 gene editing method, which enabled concurrent expression of the matrix (M), H, and F genes. The recombinant strain provided faster seroconversion than the parent strain among minks as well as provided higher rates of antibody positivity than the parent strain among foxes and minks even before the administration of a second booster vaccination. We demonstrated, for the first time, that the CRISPR/Cas9 system can be applied for the rapid and efficient modification of the ALVAC-CDV-F-H genome and also that a high-dose new recombinant strain that produces CDV VLPs may present good outcomes in the prevention of CD among foxes and minks.
- Published
- 2020
50. Adaptive amino acid substitutions enhance the virulence of a novel human H7N9 influenza virus in mice
- Author
-
Zhijun Yu, Bo Zhou, Zhiping Xia, Tiecheng Wang, Jun Qian, Yuwei Gao, Xianzhu Xia, Chengyu Wang, Yongkun Zhao, Linna Liu, and Weiyang Sun
- Subjects
0301 basic medicine ,Virulence ,Severe disease ,Genome, Viral ,Biology ,Influenza A Virus, H7N9 Subtype ,Virus Replication ,Microbiology ,Virus ,Mice ,03 medical and health sciences ,In vivo ,Serial passage ,Animals ,Humans ,chemistry.chemical_classification ,Genetics ,Mice, Inbred BALB C ,General Veterinary ,General Medicine ,Adaptation, Physiological ,Virology ,Amino acid ,030104 developmental biology ,Amino Acid Substitution ,chemistry ,Viral genomes ,Mutation ,Female - Abstract
To identify molecular features that confer enhanced H7N9 virulence in mammals, we independently generated three mouse-adapted variants of A/Shanghai/2/2013 (H7N9) by serial passage in mice. The mouse lethal doses (MLD 50 ) of the mouse-adapted variants were reduced >1000–100000-fold when compared to the parental virus. Adapted variants displayed enhanced replication kinetics in vivo , and were capable of replicating in multiple organs. Analysis of adapted viral genomes revealed a total of 14 amino acid changes among the three variant viruses in the PA (T97I, K328R, P332T, and Q556R), HA (H3 numbering; A107T, R220I, L226Q, and R354K), NP (A284T and M352I), NA (M26I, N142S, and G389D), and M1 (M128R) proteins. Notably, many of these adaptive amino acid changes have been identified in naturally occurring H7 isolates. Our results identify amino acid substitutions that collectively enhance the ability of a human H7N9 virus to replicate and cause severe disease in mice.
- Published
- 2016
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.