6,127 results on '"RNA virus infections"'
Search Results
2. Efficacy and Safety of Grazoprevir (+) Uprifosbuvir (+) Ruzasvir (MK-3682B) (MK-5172 + MK-3682 + MK-8408) Fixed Dose Combination in Chronic HCV Participants Failing Prior Antiviral Treatment (MK-3682-021)
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- 2024
3. Predicting Severity and Disease Progression in Influenza-like Illness (Including COVID-19) (PREDICT-ILI)
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- 2024
4. RCT of Vapendavir in Patients With COPD and Human Rhinovirus/Enterovirus Upper Respiratory Infection
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Virtus Respiratory Research
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- 2024
5. VRC 705: A Zika Virus DNA Vaccine in Healthy Adults and Adolescents (DNA)
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- 2024
6. Study of Interferon-Gamma in the Complex Treatment of Patients Infected With HIV and Tuberculosis (MSPB_TB)
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North-Western State Medical University named after I.I.Mechnikov
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- 2024
7. Association of antenatal and early childhood air pollution and greenspace exposures with respiratory pathogen upper airway acquisitions and respiratory health outcomes.
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Takashima, Mari D., Grimwood, Keith, Vilcins, Dwan, Knibbs, Luke D., Sly, Peter D., Lambert, Stephen B., and Ware, Robert S.
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ASTHMA risk factors , *AIR pollution , *RISK assessment , *RESPIRATORY organ sounds , *NITRIC oxide , *NATURE , *RESPIRATORY infections , *PRENATAL exposure delayed effects , *AUSTRALIANS , *MICROBIAL sensitivity tests , *SCIENTIFIC observation , *RNA virus infections , *COMMUNITIES , *REVERSE transcriptase polymerase chain reaction , *DESCRIPTIVE statistics , *LONGITUDINAL method , *PSEUDOMONADALES , *ODDS ratio , *ENVIRONMENTAL exposure , *DIARY (Literary form) , *METROPOLITAN areas , *PARTICULATE matter , *BACTERIAL diseases , *VIRUS diseases , *STREPTOCOCCAL diseases , *DATA analysis software , *CONFIDENCE intervals , *HAEMOPHILUS diseases , *PROPORTIONAL hazards models , *DISEASE incidence , *DISEASE risk factors , *CHILDREN - Abstract
The association of air pollution and greenspace with respiratory pathogen acquisition and respiratory health was investigated in a community-based birth-cohort of 158 Australian children. Weekly nasal swabs and daily symptom-diaries were collected for 2-years, with annual reviews from ages 3-7-years. Annual exposure to fine-particulate-matter (PM2.5), nitrogen-dioxide (NO2), and normalised-difference-vegetation-index (NDVI) was estimated for pregnancy and the first 2-years-of-life. We examined rhinovirus, any respiratory virus, Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae detections in the first 3-months-of-life, age at initial pathogen detection, wheezing in the first 2-years, and asthma at ages 5-7-years. Our findings suggest that higher NDVI was associated with fewer viral and M. catarrhalis detections in the first 3-months, while increased PM2.5 and NO2 were linked to earlier symptomatic rhinovirus and H. influenzae detections, respectively. However, no associations were observed with wheezing or asthma. Early-life exposure to air pollution and greenspace may influence early-life respiratory pathogen acquisition and illness. [ABSTRACT FROM AUTHOR]
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- 2024
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8. Determinants of pegivirus persistence, cross-species infection, and adaptation in the laboratory mouse.
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Nennig, Kylie, Murthy, Satyapramod, Maloney, Sara, Shaw, Teressa M., Sharobim, Mark, Matkovic, Eduard, Fadiran, Simi, Larsen, Malorie, Ramuta, Mitchell D., Kim, Arthur S., Teijaro, John R., Grove, Joe, Stremlau, Matthew, Sharma, Himanshu, Trivedi, Sheetal, Blum, Michael J., O'Connor, David H., Hyde, Jennifer L., Stapleton, Jack T., and Kapoor, Amit
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RNA virus infections , *TYPE I interferons , *CHRONIC hepatitis B , *LABORATORY mice , *TRANSGENIC animals - Abstract
Viruses capable of causing persistent infection have developed sophisticated mechanisms for evading host immunity, and understanding these processes can reveal novel features of the host immune system. One such virus, human pegivirus (HPgV), infects ~15% of the global human population, but little is known about its biology beyond the fact that it does not cause overt disease. We passaged a pegivirus isolate of feral brown rats (RPgV) in immunodeficient laboratory mice to develop a mouse-adapted virus (maPgV) that established persistent high-titer infection in a majority of wild-type laboratory mice. maRPgV viremia was detected in the blood of mice for >300 days without apparent disease, closely recapitulating the hallmarks of HPgV infection in humans. We found a pro-viral role for type-I interferon in chronic infection; a lack of PD-1-mediated tolerance to PgV infection; and multiple mechanisms by which PgV immunity can be achieved by an immunocompetent host. These data indicate that the PgV immune evasion strategy has aspects that are both common and unique among persistent viral infections. The creation of maPgV represents the first PgV infection model in wild-type mice, thus opening the entire toolkit of the mouse host to enable further investigation of this persistent RNA virus infections. Author summary: Chronic viral infections take an enormous toll on human health: over 300 million people live with chronic hepatitis B, hepatitis C, or HIV. However, animal models of chronic viral infection are largely confined to nonhuman primates. As such, the vast resources of the laboratory mouse (i.e., transgenic animals, reagents, increased statistical power) have been underutilized to study chronic viral infection. Here, we adapted a rat pegivirus (RPgV) to infect the laboratory mouse. Once adapted to this new host, the mouse-adapted pegivirus (maPgV) causes persistent high-titer viremia in wild-type (i.e., not immunocompromised) laboratory mice for hundreds of days. This new model of persistent viral infection exhibited unique properties, including a lack of disease in immunocompromised mice or mice with a hyperactive immune system. The creation of maPgV represents the first pegivirus infection model in wild-type mice, thus opening the entire toolkit of the mouse host to enable further investigation of persistent RNA infections. [ABSTRACT FROM AUTHOR]
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- 2024
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9. Detection of foot-and-mouth disease virus RNA using a closed loop-mediated isothermal amplification system.
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Edwards, Natasha, Reboud, Julien, Xiaoxiang Yan, Xin Guo, Cooper, Jonathan M., Wadsworth, Jemma, Waters, Ryan, Mioulet, Valerie, King, Donald P., and Shaw, Andrew E.
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RNA virus infections ,FOOT & mouth disease ,ANIMAL diseases ,VIRUS diseases ,COMMUNICABLE diseases - Abstract
Foot-and-mouth disease (FMD) is a highly contagious viral disease of clovenhoofed animals responsible for economic losses that amount to >$20 billion annually. Rapid recognition of FMD cases provides vital information to guide control programmes. A range of point-of-need amplification technologies have been developed which allow sensitive detection of the causative virus (FMDV) in the field at locations remote from laboratories. Here we describe a novel system to detect FMDV RNA using loop-mediated isothermal amplification (LAMP). This test was evaluated using a panel of FMDV isolates (n = 79) and RNA standards demonstrating capability to amplify viral genome directly from clinical material in the absence of nucleic acid extraction. This extraction-free RT-LAMP assay was transferred to a bespoke closed-system lateral flow test (LFT) that was used in combination with a low-cost hand-held heater. Our results show that the RT-LAMP-LFT assay retains a high level of diagnostic and analytical sensitivity when using direct clinical material, with a limit of detection under 80 copies per reaction. Together, our data support the potential for the use of this assay at the point-of-need to facilitate rapid feedback on the status of suspect cases. [ABSTRACT FROM AUTHOR]
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- 2024
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10. Phosphorylation of the selective autophagy receptor TAX1BP1 by TBK1 and IKBKE/IKKi promotes ATG8-family protein-dependent clearance of MAVS aggregates.
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White, Jesse, Choi, Young Bong, Zhang, Jiawen, Vo, Mai Tram, He, Chaoxia, Shaikh, Kashif, and Harhaj, Edward W.
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RNA virus infections , *VESICULAR stomatitis , *VIRUS diseases , *LYSOSOMES , *AUTOPHAGY - Abstract
TAX1BP1 is a selective macroautophagy/autophagy receptor that inhibits NFKB and RIGI-like receptor (RLR) signaling to prevent excessive inflammation and maintain homeostasis. Selective autophagy receptors such as SQSTM1/p62 and OPTN are phosphorylated by the kinase TBK1 to stimulate their selective autophagy function. However, it is unknown if TAX1BP1 is regulated by TBK1 or other kinases under basal conditions or during RNA virus infection. Here, we found that TBK1 and IKBKE/IKKi function redundantly to phosphorylate TAX1BP1 and regulate its autophagic turnover through canonical macroautophagy. TAX1BP1 phosphorylation promotes its localization to lysosomes, resulting in its degradation. Additionally, we found that during vesicular stomatitis virus infection, TAX1BP1 is targeted to lysosomes in an ATG8-family protein-independent manner. Furthermore, TAX1BP1 plays a critical role in the clearance of MAVS aggregates, and phosphorylation of TAX1BP1 controls its MAVS aggrephagy function. Together, our data support a model whereby TBK1 and IKBKE license TAX1BP1-selective autophagy function to inhibit MAVS and RLR signaling.
Abbreviations: ATG: autophagy related; BafA1: bafilomycin A1; CALCOCO2: calcium binding and coiled-coil domain 2; GFP: green fluorescent protein; IFA: indirect immunofluorescence assay; IFN: interferon; IκB: inhibitor of nuclear factor kappa B; IKK: IκB kinase; IRF: interferon regulatory factor; KO: knockout; LAMP1: lysosomal associated membrane protein 1; LIR: LC3-interacting region; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAVS: mitochondrial antiviral signaling protein; MEF: mouse embryonic fibroblast; MOI: multiplicity of infection; IKBKG/NEMO: inhibitor of nuclear factor kappa B kinase regulatory subunit gamma; NFKB: nuclear factor kappa B; OPTN: optineurin; Poly(I:C): polyinosinic-polycytidylic acid; RB1CC1/FIP200: RB1 inducible coiled-coil 1; RIGI: RNA sensor RIG-I; RLR: RIGI-like receptor; SDD-AGE: semi-denaturing detergent-agarose gel electrophoresis; SeV: Sendai virus; SLR: SQSTM1-like receptor; SQSTM1: sequestosome 1; TAX1BP1: Tax1 binding protein 1; TBK1: TANK binding kinase 1; TNF: tumor necrosis factor; TRAF: TNF receptor associated factor; VSV: vesicular stomatitis virus; ZnF: zinc finger. [ABSTRACT FROM AUTHOR]- Published
- 2024
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11. MAVS Cys508 palmitoylation promotes its aggregation on the mitochondrial outer membrane and antiviral innate immunity.
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Yinong Liu, Dan Hou, Wenzhe Chen, Xuan Lu, Komaniecki, Garrison P., Yilai Xu, Tao Yu, Zhang, Sophia M., Linder, Maurine E., and Hening Lin
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RNA virus infections , *VIRAL proteins , *MITOCHONDRIAL membranes , *MEMBRANE proteins , *NATURAL immunity - Abstract
Cysteine palmitoylation or S-palmitoylation catalyzed by the ZDHHC family of acyltransferases regulates the biological function of numerous mammalian proteins as well as viral proteins. However, understanding of the role of S-palmitoylation in antiviral immunity against RNA viruses remains very limited. The adaptor protein MAVS forms functionally essential prion-like aggregates upon activation by viral RNA-sensing RIG-I-like receptors. Here, we identify that MAVS, a C-terminal tail-anchored mitochondrial outer membrane protein, is S-palmitoylated by ZDHHC7 at Cys508, a residue adjacent to the tail-anchor transmembrane helix. Using superresolution microscopy and other biochemical techniques, we found that the mitochondrial localization of MAVS at resting state mainly depends on its transmembrane tail-anchor, without regulation by Cys508 S-palmitoylation. However, upon viral infection, MAVS S-palmitoylation stabilizes its aggregation on the mitochondrial outer membrane and thus promotes subsequent propagation of antiviral signaling. We further show that inhibition of MAVS S-palmitoylation increases the host susceptibility to RNA virus infection, highlighting the importance of S-palmitoylation in the antiviral innate immunity. Also, our results indicate ZDHHC7 as a potential therapeutic target for MAVS-related autoimmune diseases. [ABSTRACT FROM AUTHOR]
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- 2024
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12. PRRSV hijacks DDX3X protein and induces ferroptosis to facilitate viral replication.
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Mao, Qian, Ma, Shengming, Li, Shuangyu, Zhang, Yuhua, Li, Shanshan, Wang, Wenhui, Wang, Fang, Guo, Zekun, and Wang, Chengbao
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RNA virus infections ,GENE expression ,RNA helicase ,GENE silencing ,TRANSMISSION electron microscopy ,RNA metabolism - Abstract
Porcine reproductive and respiratory syndrome virus (PRRSV) is a severe disease with substantial economic consequences for the swine industry. The DEAD-box helicase 3 (DDX3X) is an RNA helicase that plays a crucial role in regulating RNA metabolism, immunological response, and even RNA virus infection. However, it is unclear whether it contributes to PRRSV infection. Recent studies have found that the expression of DDX3X considerably increases in Marc-145 cells when infected with live PRRSV strains Ch-1R and SD16; however, it was observed that inactivated viruses did not lead to any changes. By using the RK-33 inhibitor or DDX3X-specific siRNAs to reduce DDX3X expression, there was a significant decrease in the production of PRRSV progenies. In contrast, the overexpression of DDX3X in host cells substantially increased the proliferation of PRRSV. A combination of transcriptomics and metabolomics investigations revealed that in PRRSV-infected cells, DDX3X gene silencing severely affected biological processes such as ferroptosis, the FoxO signalling pathway, and glutathione metabolism. The subsequent transmission electron microscopy (TEM) imaging displayed the typical ferroptosis features in PRRSV-infected cells, such as mitochondrial shrinkage, reduction or disappearance of mitochondrial cristae, and cytoplasmic membrane rupture. Conversely, the mitochondrial morphology was unchanged in DDX3X-inhibited cells. Furthermore, silencing of the DDX3X gene changed the expression of ferroptosis-related genes and inhibited the virus proliferation, while the drug-induced ferroptosis inversely promoted PRRSV replication. In summary, these results present an updated perspective of how PRRSV infection uses DDX3X for self-replication, potentially leading to ferroptosis via various mechanisms that promote PRRSV replication. [ABSTRACT FROM AUTHOR]
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- 2024
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13. Master Regulators of Causal Networks in Intestinal- and Diffuse-Type Gastric Cancer and the Relation to the RNA Virus Infection Pathway.
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Tanabe, Shihori, Quader, Sabina, Cabral, Horacio, Perkins, Edward J., Yokozaki, Hiroshi, and Sasaki, Hiroki
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RNA virus infections , *CANCER stem cells , *GENE expression , *GENE regulatory networks , *STOMACH cancer - Abstract
Causal networks are important for understanding disease signaling alterations. To reveal the network pathways affected in the epithelial–mesenchymal transition (EMT) and cancer stem cells (CSCs), which are related to the poor prognosis of cancer, the molecular networks and gene expression in diffuse- and intestinal-type gastric cancer (GC) were analyzed. The network pathways in GC were analyzed using Ingenuity Pathway Analysis (IPA). The analysis of the probe sets in which the gene expression had significant differences between diffuse- and intestinal-type GC in RNA sequencing of the publicly available data identified 1099 causal networks in diffuse- and intestinal-type GC. Master regulators of the causal networks included lenvatinib, pyrotinib, histone deacetylase 1 (HDAC1), mir-196, and erb-b2 receptor tyrosine kinase 2 (ERBB2). The analysis of the HDAC1-interacting network identified the involvement of EMT regulation via the growth factors pathway, the coronavirus pathogenesis pathway, and vorinostat. The network had RNA–RNA interactions with microRNAs such as mir-10, mir-15, mir-17, mir-19, mir-21, mir-223, mir-25, mir-27, mir-29, and mir-34. The molecular networks revealed in the study may lead to identifying drug targets for GC. [ABSTRACT FROM AUTHOR]
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- 2024
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14. MHCI trafficking signal‐based mRNA vaccines strengthening immune protection against RNA viruses.
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Zhang, Yupei, Zhai, Songhui, Qin, Shugang, Chen, Yuting, Chen, Kepan, Huang, Zhiying, Lan, Xing, Luo, Yaoyao, Li, Guohong, Li, Hao, He, Xi, Chen, Meiwan, Zhang, Zhongwei, Peng, Xingchen, Jiang, Xin, Huang, Hai, and Song, Xiangrong
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RNA virus infections , *MAJOR histocompatibility complex , *TRAFFIC signs & signals , *B cells , *RNA viruses , *T cells - Abstract
The major histocompatibility complex class I (MHCI) trafficking signal (MITD) plays a pivotal role in enhancing the efficacy of mRNA vaccines. However, there was a lack of research investigating its efficacy in enhancing immune responses to RNA virus infections. Here, we have developed an innovative strategy for the formulation of mRNA vaccines. This approach involved the integration of MITD into the mRNA sequence encoding the virus antigen. Mechanistically, MITD‐based mRNA vaccines can strengthen immune protection by mimicking the dynamic trafficking properties of MHCI molecule and thus expand the memory specific B and T cells. The model MITD‐based mRNA vaccines encoding binding receptor‐binding domain (RBD) of SARS‐CoV‐2 were indeed found to achieve protective duration, optimal storage stability, broad efficacy, and high safety. [ABSTRACT FROM AUTHOR]
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- 2024
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15. Design of novel broad‐spectrum antiviral nucleoside analogues using natural bases ring‐opening strategy.
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Du, Xingyi, Yang, Xingxing, Zhao, Jianyuan, Zhang, Jinyan, Yu, Jiahui, Ma, Ling, Zhang, Weina, Cen, Shan, Ren, Xuhong, and He, Xinhua
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RNA virus infections , *VESICULAR stomatitis , *RNA polymerases , *INFLUENZA A virus , *BASE pairs - Abstract
The global prevalence of RNA virus infections has presented significant challenges to public health in recent years, necessitating the expansion of its alternative therapeutic library. Due to its evolutional conservation, RNA‐dependent RNA polymerase (RdRp) has emerged as a potential target for broad‐spectrum antiviral nucleoside analogues. However, after over half a century of structural modification, exploring unclaimed chemical space using frequently‐used structural substitution methods to design new nucleoside analogues is challenging. In this study, we explore the use of the "ring‐opening" strategy to design new base mimics, thereby using these base mimics to design new nucleoside analogues with broad‐spectrum antiviral activities. A total of 29 compounds were synthesized. Their activity against viral RdRp was initially screened using an influenza A virus RdRp high‐throughput screening model. Then, the antiviral activity of 38a was verified against influenza virus strain A/PR/8/34 (H1N1), demonstrating a 50% inhibitory concentration (IC50) value of 9.95 μM, which was superior to that of ribavirin (the positive control, IC50 = 11.43 μM). Moreover, 38a also has inhibitory activity against coronavirus 229E with an IC50 of 30.82 μM. In addition, compounds 42 and 46f exhibit an 82% inhibition rate against vesicular stomatitis virus at a concentration of 20 μM and hardly induce cytotoxicity in host cells. This work demonstrates the feasibility of designing nucleoside analogues with "ring‐opening" bases and suggests the "ring‐opening" nucleosides may have greater polarity, and designing prodrugs is an important aspect of optimizing their antiviral activity. Future research should focus on enhancing the conformational restriction of open‐loop bases to mimic Watson‐Crick base pairing better and improve antiviral activity. [ABSTRACT FROM AUTHOR]
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- 2024
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16. TRIM38 Induced in Respiratory Syncytial Virus-infected Cells Downregulates Type I Interferon Expression by Competing with TRIM25 to Bind RIG-I.
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Sun, Qingqing, Han, Xiao, Meng, Lingtong, Li, Hongru, Chen, Yijia, Yin, Lizheng, Wang, Chang, Wang, Jiachao, Li, Miao, Gao, Xue, Li, Wenjian, Wei, Lin, and Ma, Cuiqing
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RNA virus infections , *TYPE I interferons , *BINDING sites , *RESPIRATORY syncytial virus , *UBIQUITINATION - Abstract
Innate immune response is the first line of defense for the host against virus invasion. One important response is the synthesis and secretion of type I interferon (IFN-I) in the virus-infected host cells. Here, we found that respiratory syncytial virus (RSV) infection induced high expression of TRIM25, which belongs to the tripartite motif-containing (TRIM) family of proteins. TRIM25 bound and activated retinoic acid-inducible gene I (RIG-I) by K63-linked ubiquitination. Accordingly, RIG-I mediated the production of IFN-I mainly through the nuclear factor kappa-B (NF-κB) pathway in respiratory epithelial cells. Interestingly, IFN-I, in turn, promoted a high expression of TRIM38 which downregulated the expression of IFN-I by reducing the protein level of RIG-I by K48-linked ubiquitination. More importantly, the binding site of TRIM25 to RIG-I was found in the narrow 25th-43rd amino acid (aa) region of RIG-I N-terminus. In contrast, the binding sites of TRIM38 to RIG-I were found in a much wider amino acid region, which included the binding site of TRIM25 on RIG-I. As a result, TRIM38 inhibits the production of IFN-I by competing with TRIM25 for RIG-I binding. Thus, TRIM38 negatively regulates RIG-I activation to, in turn, downregulate IFN-I expression, thus interfering with host immune response. A negative feedback loop effectively "puts the brakes" on the reaction once host immune response is overactivated and homeostasis is unbalanced. We also discovered that TRIM25 bound RIG-I by a new K63-linked ubiquitination located at K-45 of the first caspase recruitment domain (CARD). Collectively, these results confirm an antagonism between TRIM38 and TRIM25 in regulating IFN-I production by affecting RIG-I activity following RNA virus infection. [ABSTRACT FROM AUTHOR]
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- 2024
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17. Molecular Cloning, Tissue Distribution and Antiviral Immune Response of Duck Src.
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Liu, Jinlu, Luo, Shuwen, Wang, Guoyao, Hu, Xuming, Chen, Guohong, and Xu, Qi
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RNA virus infections , *NEWCASTLE disease virus , *AVIAN influenza A virus , *AMINO acid residues , *IMMUNOREGULATION - Abstract
As a founding member of the Src family of kinases, Src has been confirmed to participate in the regulation of immune responses, integrin signaling, and motility. Ducks are usually asymptomatic carriers of RNA viruses such as Newcastle disease virus and avian influenza virus, which can be deadly to chickens. The beneficial role of Src in modulating the immune response remains largely unknown in ducks. Here, we characterized the duck Src and found that it contains a 192-base-pair 5′ untranslated region, a 1602-base-pair coding region, and a 2541-base-pair 3′ untranslated region, encoding 533 amino acid residues. Additionally, duSrc transcripts were significantly activated in duck tissues infected by Newcastle disease virus compared to controls. The duSrc transcripts were notably widespread in all tissues examined, and the expression level was higher in liver, blood, lung, pancreas, and thymus. Moreover, we found the expression levels of IFN-β, NF-κB, IRF3, and Src were significantly increased in DEFs after infection with 5′ppp dsRNA, but there was no significant difference before and after treatment in DF1 cells. Furthermore, overexpression of duSrc followed by stimulation with 5′ppp dsRNA led to an elevation of IFN-β levels. The SH3 and PTKc domains of duSrc contributed to promoting the activity of IFN-β and NF-κB in DEFs stimulated by 5′ppp dsRNA. [ABSTRACT FROM AUTHOR]
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- 2024
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18. WHO's Health Emergencies Programme: acute emergencies monthly summary -- June 2024.
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PREVENTION of epidemics , *HEALTH services accessibility , *DEATH , *RNA virus infections , *CHOLERA , *GOAL (Psychology) , *H5N1 Influenza , *WAR , *WORLD health , *CLINICAL pathology , *MEDICAL emergencies , *CONVALESCENCE , *MEDICAL research , *COMMUNICATION , *MONKEYPOX , *REPORT writing , *PUBLIC health , *EMERGENCY management , *REFUGEES , *INFECTIOUS disease transmission - Abstract
The article presents a summary of disease outbreak news reports received by the World Health Organization's Heath Emergencies Programme for June 2024. It includes a case of human infection with avian influenza A virus in a patient in Mexico, a national outbreak of mpox in the Democratic Republic of Congo, and outbreaks of Oropouche virus disease in Cuba.
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- 2024
19. Clinic-based ART Diagnostic Evaluation (CLADE)
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US Military HIV Research Program and Kenya Medical Research Institute
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- 2023
20. Integrating Enhanced HIV PrEP Into a STI Clinic in Lilongwe
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- 2023
21. Development of a Novel Plasmid-based Eukaryotic Model to Investigate Crimean-Congo Hemorrhagic Fever Virus
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Nesibe Selma GÜLER ÇETİN, Özlem BAKANGİL, Merve KALKAN YAZICI, Sercan KESKİN, and Mehmet Ziya DOYMAZ
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crimean-congo hemorrhagic fever virus ,virus-like particle ,vaccines ,bunyavirus ,rna virus infections ,immunology ,Medicine (General) ,R5-920 - Abstract
Objective: Crimean-Congo Hemorrhagic Fever (CCHF) is a severe tick-borne viral disease, caused by the Crimean-Congo Hemorrhagic Fever virus (CCHFV). The global expansion of CCHF and high mortality rates underline the critical need for research and development of effective treatments and vaccines. However, the high risk of transmission and requirement for highcontainment facilities hinder investigations involving live virus. In this study, we aimed to address these challenges by employing a plasmid-based virus-like particle (VLP) system and a minigenome model to investigate the biology and immunology of CCHFV. Methods: The plasmids encoding CCHFV structural genes of CCHFV were transfected into Huh-7 cells. Viral protein expression was confirmed using fluorescence imaging, immunological and molecular methods. A minigenome system was developed, eliminating the need for T7 polymerase, T7-expressing cellular lines, or viral ribonuclear protein complexes, allowing autonomous virus replication without a helper virus or transfections using plasmids in trans. Results: Fluorescence microscopy showed successful production of NP-EGFP and GC-EGFP proteins with various subcellular localizations. Western blot analysis demonstrated the presence of pre-Gc, Gc, pre-Gn, Gn, and Np proteins in cell lysates and supernatants. ELISA analysis suggested that transfection of Np alone, in combination with Gc, or all three proteins might cause distinct VLP formations. Huh-7 cells successfully expressed reporter genes after transfection of minigenome RNA transcripts. Conclusion: The study advances CCHFV research by using novel tools for virus biology and immunology. The findings may provide new avenues for research that promise better public health preparation against this neglected viral disease.
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- 2024
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22. The seroprevalence of antibodies to Japanese encephalitis virus in five New South Wales towns at high risk of infection, 2022: a cross‐sectional serosurvey.
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Baldwin, Zoe, Hueston, Linda, Roberts‐Witteveen, April, Stanley, Priscilla, Sheel, Meru, Winkler, Noni, Koirala, Archana, Macartney, Kristine, Case, Jennifer, Hope, Kirsty, and Glasgow, Keira M
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Objectives: To determine the proportion of people in New South Wales towns at high risk of Japanese encephalitis virus (JEV) infections during the 2022 outbreak; to identify risk factors for JEV infection. Study design: Cross‐sectional serosurvey study of the seroprevalence of JEV‐specific antibodies in NSW. Setting, participants: Convenience sample of people (all ages) from five regional NSW towns deemed to be at high risk of JEV infections after first outbreak of Japanese encephalitis in southeastern Australia in early 2022 (Balranald, Corowa, Dubbo, Griffith, Temora), 21 June – 22 July 2022. Main outcome measures: Proportion of people seropositive for JEV total antibody, assayed by defined epitope‐blocking enzyme‐linked immunosorbent assay; prevalence odds ratios for exposure risk factors and protective behaviours. Results: Eighty of 917 eligible participants (559 girls or women, 61%; 42 Aboriginal and Torres Strait Islander people, 4.6%; median age, 52 years [IQR, 37–62 years]) were seropositive for JEV‐specific total antibody (8.7%); the median age of seropositive people was 61 years (IQR, 48–70 years). The seropositivity proportion was largest for people aged 65 years or more (30 of 192; weighted proportion, 13.7%) and larger for male than female participants (30 of 358, 10.6% v 50 of 559, 7.5%). Five of 42 samples from Aboriginal and Torres Strait Islander participants were seropositive (12%). We found mixed associations with a range of potential risk factors. Conclusion: We found evidence for a substantial number of JEV infections in five regional NSW towns during a single arbovirus season in 2022. Public health responses, including effective surveillance, vaccination against JEV, and mosquito management, are critical for controlling outbreaks. Promoting behaviours that reduce exposure to mosquitoes is a core component of prevention, particularly when the vaccine supply is limited. [ABSTRACT FROM AUTHOR]
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- 2024
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23. Evaluation of hepatitis E virus RNA persistence in experimentally contaminated cured pork liver sausages.
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Lorusso, Patrizio, Pandiscia, Annamaria, Manfredi, Alessio, Tantillo, Giuseppina Marilia, and Terio, Valentina
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HEPATITIS E virus , *RNA viruses , *RNA virus infections , *MEAT industry , *PORK , *SAUSAGES , *ANIMAL industry - Abstract
Hepatitis E is a disease sustained by RNA viruses, which have four different genotypes, all of which are responsible for acute forms of hepatitis. Genotypes 1 and 2 infect only humans, causing epidemics mainly transmitted by contaminated water, while genotypes 3 and 4 are zoonotic, and the infection is linked to the consumption of raw or undercooked meat or meat products. Hepatitis E virus (HEV) genotypes 3 and 4 have been detected in domestic Suidae, considered the asymptomatic reservoir of HEV, and in wild animals such as wild boar and deer. Despite scientific studies that have highlighted the presence of HEV in cured meat products, such as pork liver sausages, the viral persistence in the different production steps of curing has not been evaluated. Therefore, this study aimed to evaluate the persistence of HEV genotype 3 during the different curing and storage times of experimentally contaminated pork liver sausages using biomolecular methods. The sausages tested positive at all curing and storage times. This study confirms the potential risk attributed to pork liver sausages in HEV transmission. However, to guarantee an efficient risk assessment, future studies will be performed to correlate the presence of HEV RNA with infectious viral particles. [ABSTRACT FROM AUTHOR]
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- 2024
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24. Stimulator of Interferon Gene Agonists Induce an Innate Antiviral Response against Influenza Viruses.
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Lee, Hyun Jung, Park, Joo-Hoo, Park, Il-Ho, and Shin, Ok Sarah
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INFLUENZA viruses , *RNA virus infections , *VIRUS diseases , *ANTIVIRAL agents , *INTERFERONS , *EPITHELIAL cell culture , *TYPE I interferons - Abstract
The devastating effects of COVID-19 have highlighted the importance of prophylactic and therapeutic strategies to combat respiratory diseases. Stimulator of interferon gene (STING) is an essential component of the host defense mechanisms against respiratory viral infections. Although the role of the cGAS/STING signaling axis in the innate immune response to DNA viruses has been thoroughly characterized, mounting evidence shows that it also plays a key role in the prevention of RNA virus infections. In this study, we investigated the role of STING activation during Influenza virus (IFV) infection. In both mouse bone marrow-derived macrophages and monocytic cell line THP-1 differentiated with PMA, we found that dimeric amidobenzimidazole (diABZI), a STING agonist, had substantial anti-IFV activity against multiple strains of IFV, including A/H1N1, A/H3N2, B/Yamagata, and B/Victoria. On the other hand, a pharmacological antagonist of STING (H-151) or the loss of STING in human macrophages leads to enhanced viral replication but suppressed IFN expression. Furthermore, diABZI was antiviral against IFV in primary air–liquid interface cultures of nasal epithelial cells. Our data suggest that STING agonists may serve as promising therapeutic antiviral agents to combat IFV. [ABSTRACT FROM AUTHOR]
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- 2024
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25. Safety and Immunogenicity of an mRNA-Based hMPV/PIV3 Combination Vaccine in Seropositive Children.
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Schnyder Ghamloush, Sabine, Essink, Brandon, Bo Hu, Kalidindi, Shiva, Morsy, Louie, Egwuenu-Dumbuya, Chioma, Kapoor, Archana, Girard, Bethany, Dhar, Rakesh, Lackey, Rebecca, Snape, Matthew D., and Shaw, Christine A.
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IMMUNOGLOBULIN analysis , *PATIENT safety , *PLACEBOS , *RESEARCH funding , *VACCINE effectiveness , *RNA virus infections , *STATISTICAL sampling , *SHIVERING , *RANDOMIZED controlled trials , *INJECTIONS , *VACCINE immunogenicity , *VIRAL vaccines , *PAIN , *DROWSINESS , *MEMBRANE proteins , *DRUG tolerance , *EVALUATION , *CHILDREN - Abstract
OBJECTIVES: Human metapneumovirus (hMPV) and parainfluenza virus type 3 (PIV3) are common respiratory illnesses in children. The safety and immunogenicity of an investigational mRNA-based vaccine, mRNA-1653, encoding membrane-anchored fusion proteins of hMPV and PIV3, was evaluated in hMPV/PIV3-seropositive children. METHODS: In this phase 1b randomized, observer-blind, placebo-controlled, dose-ranging study, hMPV/PIV3-seropositive children were enrolled sequentially into 2 dose levels of mRNA-1653 administered 2 months apart; children aged 12 to 36 months were randomized (1:1) to receive 10-mg of mRNA-1653 or placebo and children aged 12 to 59 months were randomized (3:1) to receive 30-mg of mRNA-1653 or placebo. RESULTS: Overall, 27 participants aged 18 to 55 months were randomized; 15 participants received 10-µg of mRNA-1653 (n = 8) or placebo (n = 7), whereas 12 participants received 30-µg of mRNA-1653 (n = 9) or placebo (n = 3). mRNA-1653 was well-tolerated at both dose levels. The only reported solicited local adverse reaction was tenderness at injection site; solicited systemic adverse reactions included grade 1 or 2 chills, irritability, loss of appetite, and sleepiness. A single 10-µg or 30-µg mRNA-1653 injection increased hMPV and PIV3 neutralizing antibody titers (geometric mean fold-rise ratio over baseline: hMPV-A = 2.9-6.1; MPV-B = 6.2-13.2; PIV3 = 2.8-3.0) and preF and postF binding antibody concentrations (geometric mean fold-rise ratio: hMPV preF 5 5.3-6.1; postF = 4.6-6.5 and PIV3 preF = 13.9-14.2; postF = 11.0-12.1); second injection did not further increase antibody levels in these seropositive children. Binding antibody responses were generally preF biased. CONCLUSIONS: mRNA-1653 was well-tolerated and boosted hMPV and PIV3 antibody levels in seropositive children aged 12 to 59 months, supporting the continued development of mRNA- 1653 or its components for the prevention of hMPV and PIV3. [ABSTRACT FROM AUTHOR]
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- 2024
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26. LTN1 promotes RLR degradation to inhibit immune response to RNA virus through the ESCRT pathway.
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Qin, Fei, Cai, Baoshan, Wang, Peng, Cao, Runyu, Zhang, Yuling, Wen, Hongling, Zheng, Yi, Zhao, Wei, Gao, Chengjiang, and Liu, Bingyu
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IMMUNE response ,RNA virus infections ,DNA helicases ,DOUBLE-stranded RNA ,INTERFERON receptors ,RNA viruses ,VESICULAR stomatitis ,SENDAI virus - Abstract
The excessive activation of immune responses will trigger autoimmune diseases or inflammatory injury. The endosomal sorting complexes required for transport (ESCRT) system can capture and mediate ubiquitinated protein degradation, which timely terminates signaling pathway hyperactivation. However, whether the ESCRT system participates in regulating RIGI-like receptor (RLR)-mediated antiviral responses remains unknown. In this study, we show that LTN1/listerin, a major component of RQC, can recruit E3 ubiquitin ligase TRIM27 to trigger K63-linked polyubiquitination of RIGI and IFIH1/MDA5. This K63-linked polyubiquitination facilitates the sorting and degradation of RIGI and IFIH1 proteins through the ESCRT-dependent pathway. Concordantly, LTN1 deficiency enhances the innate antiviral response to infection with RNA viruses. Thus, our work uncovers a new mechanism for RIGI and IFIH1 degradation and identifies the role of LTN1 in negatively regulating RLR-mediated antiviral innate immunity, which may provide new targets for the intervention of viral infection. Abbreviation: 5'-pppRNA: 5' triphosphate double stranded RNA; ATG5: autophagy related 5; ATG7: autophagy related 7; BafA1: bafilomycin A
1 ; ESCRT: endosomal sorting complexes required for transport; CHX: cycloheximide; IFIH1/MDA5: interferon induced with helicase C domain 1; IFN: interferon; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; RIGI: RNA sensor RIG-I; RLR: RIGI-like receptors; RQC: ribosome-associated protein quality control; SeV: Sendai virus; TRIM27: tripartite motif-containing 27; VSV: vesicular stomatitis virus; VPS4: vacuolar protein sorting 4. [ABSTRACT FROM AUTHOR]- Published
- 2024
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27. Dampening of ISGylation of RIG-I by ADAP regulates type I interferon response of macrophages to RNA virus infection.
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Wang, Yan, Feng, Haixia, Li, Xiao, Ruan, Yina, Guo, Yueping, Cui, Xinxing, Zhang, Pengchao, Li, Yanli, Wang, Xinning, Wang, Xingran, Wei, Luxin, Yi, Yulan, Zhang, Lifeng, Yang, Xiaodong, and Liu, Hebin
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RNA virus infections , *MACROPHAGES , *TYPE I interferons , *GENE expression , *VIRUS diseases , *ADAPTOR proteins , *INTERFERONS , *MOSAIC viruses - Abstract
While macrophage is one of the major type I interferon (IFN-I) producers in multiple tissues during viral infections, it also serves as an important target cell for many RNA viruses. However, the regulatory mechanism for the IFN-I response of macrophages to respond to a viral challenge is not fully understood. Here we report ADAP, an immune adaptor protein, is indispensable for the induction of the IFN-I response of macrophages to RNA virus infections via an inhibition of the conjugation of ubiquitin-like ISG15 (ISGylation) to RIG-I. Loss of ADAP increases RNA virus replication in macrophages, accompanied with a decrease in LPS-induced IFN-β and ISG15 mRNA expression and an impairment in the RNA virus-induced phosphorylation of IRF3 and TBK1. Moreover, using Adap-/- mice, we show ADAP deficiency strongly increases the susceptibility of macrophages to RNA-virus infection in vivo. Mechanically, ADAP selectively interacts and functionally cooperates with RIG-I but not MDA5 in the activation of IFN-β transcription. Loss of ADAP results in an enhancement of ISGylation of RIG-I, whereas overexpression of ADAP exhibits the opposite effect in vitro, indicating ADAP is detrimental to the RNA virus-induced ISGylation of RIG-I. Together, our data demonstrate a novel antagonistic activity of ADAP in the cell-intrinsic control of RIG-I ISGylation, which is indispensable for initiating and sustaining the IFN-I response of macrophages to RNA virus infections and replication. Author summary: Macrophages are the major type I interferons (IFNs-I) producers upon virus infections, but they are also important target cells for many RNA viruses. Understanding how the IFN-I response of macrophages to RNA virus infection and replication is vital for the development of targeted therapies to mitigate severe viral diseases. To this end, the present study portrays a novel regulatory mechanism whereby ADAP exhibits a virus-suppressive function via dampening of RIG-I ISGylation in the induction of the IFN-I response of macrophages to RNA virus infections. Loss of ADAP dampens RIG-I-type I IFN signaling and renders macrophages more susceptible to virus infection. Therefore, this study provides a new insight into how the permissiveness of macrophages to RNA viruses can be controlled. Additionally, ADAP-RIG-I module can potentially serve as a novel target for therapeutic intervention against diseases caused by RNA viruses. [ABSTRACT FROM AUTHOR]
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- 2024
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28. Condensation of RNase L promotes its rapid activation in response to viral infection in mammalian cells.
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Cusic, Renee and Burke, James M.
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VIRUS diseases ,RNA virus infections ,WEST Nile virus ,DOUBLE-stranded RNA ,CONDENSATION ,DENGUE viruses - Abstract
Oligoadenylate synthetase 3 (OAS3) and ribonuclease L (RNase L) are components of a pathway that combats viral infection in mammals. Upon detection of viral double-stranded RNA (dsRNA), OAS3 synthesizes 2′-5′-oligo(A), which activates the RNase domain of RNase L by promoting the homodimerization and oligomerization of RNase L monomers. Activated RNase L rapidly degrades all cellular mRNAs, shutting off several cellular processes. We sought to understand the molecular mechanisms underlying the rapid activation of RNase L in response to viral infection. Through superresolution microscopy and live-cell imaging, we showed that OAS3 and RNase L concentrated into higher-order cytoplasmic complexes known as dsRNA-induced foci (dRIF) in response to dsRNA or infection with dengue virus, Zika virus, or West Nile virus. The concentration of OAS3 and RNase L at dRIF corresponded with the activation of RNase L–mediated RNA decay. We showed that dimerized/oligomerized RNase L concentrated in a liquid-like shell surrounding a core OAS3-dRIF structure and dynamically exchanged with the cytosol. These data establish that the condensation of dsRNA, OAS3, and RNase L into dRIF is a molecular switch that promotes the rapid activation of RNase L upon detection of dsRNA in mammalian cells. Editor's summary: Detection of viral double-stranded RNA by OAS3 rapidly induces the activation of RNase L, which results in the degradation of all cellular RNA. Cusic and Burke investigated the regulation of RNase L activation in mammalian cells. Double-stranded RNA or infection with RNA viruses, such as dengue, Zika, or West Nile virus, induced the condensation of OAS3 and active RNase L into cytoplasmic granules. These granules were composed of an OAS3–double-stranded RNA core surrounded by a shell of RNase L, which dynamically exchanged with a cytoplasmic pool. In addition to rapidly activating RNase L, the condensation of RNase L and OAS3 may also set a threshold to prevent spurious activation and the shutdown of cellular processes that occur with mRNA degradation. —Wei Wong [ABSTRACT FROM AUTHOR]
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- 2024
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29. TRIM25 predominately associates with anti-viral stress granules.
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Shang, Zehua, Zhang, Sitao, Wang, Jinrui, Zhou, Lili, Zhang, Xinyue, Billadeau, Daniel D., Yang, Peiguo, Zhang, Lingqiang, Zhou, Fangfang, Bai, Peng, and Jia, Da
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STRESS granules ,RNA virus infections ,PHASE separation ,CELLULAR signal transduction ,ANTIVIRAL agents - Abstract
Stress granules (SGs) are induced by various environmental stressors, resulting in their compositional and functional heterogeneity. SGs play a crucial role in the antiviral process, owing to their potent translational repressive effects and ability to trigger signal transduction; however, it is poorly understood how these antiviral SGs differ from SGs induced by other environmental stressors. Here we identify that TRIM25, a known driver of the ubiquitination-dependent antiviral innate immune response, is a potent and critical marker of the antiviral SGs. TRIM25 undergoes liquid-liquid phase separation (LLPS) and co-condenses with the SG core protein G3BP1 in a dsRNA-dependent manner. The co-condensation of TRIM25 and G3BP1 results in a significant enhancement of TRIM25's ubiquitination activity towards multiple antiviral proteins, which are mainly located in SGs. This co-condensation is critical in activating the RIG-I signaling pathway, thus restraining RNA virus infection. Our studies provide a conceptual framework for better understanding the heterogeneity of stress granule components and their response to distinct environmental stressors. Different environmental stressors induce different subtypes of stress granules (SGs), and each of them presumably have distinct functions. Here the authors provide a framework for understanding the compositional and functional heterogeneity of SGs, and see that TRIM25 mainly associates with anti-viral SGs. [ABSTRACT FROM AUTHOR]
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- 2024
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30. Real-time investigation of an influenza A(H3N2) virus outbreak in a refugee community, November 2022.
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Galli, C., Mazzola, G., Arosio, M., Pellegrinelli, L., Boldrini, A., Guarneri, D., Lombarda, E., Farina, C., Cereda, D., and Pariani, E.
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INFLUENZA prevention , *INFLUENZA epidemiology , *RESPIRATORY syncytial virus , *PHYLOGENY , *INFLUENZA vaccines , *RNA virus infections , *COMMUNITIES , *RESPIRATORY syncytial virus infections , *REVERSE transcriptase polymerase chain reaction , *DESCRIPTIVE statistics , *DISEASE prevalence , *RNA viruses , *NUCLEOTIDES , *EPIDEMICS , *INFLUENZA A virus, H3N2 subtype , *COMPARATIVE studies , *INFLUENZA A virus , *REFUGEES , *VACCINATION status , *IMMUNOMODULATORS , *SEQUENCE analysis - Abstract
To report epidemiological and virological results of an outbreak investigation of influenza-like illness (ILI) among refugees in Northern Italy. Outbreak investigation of ILI cases observed among nearly 100 refugees in Northern Italy unvaccinated for influenza. An epidemiological investigation matched with a differential diagnosis was carried out for each sample collected from ILI cases to identify 10 viral pathogens (SARS-CoV-2, influenza virus type A and B, respiratory syncytial virus, metapneumovirus, parainfluenza viruses, rhinovirus, enterovirus, parechovirus, and adenovirus) by using specific real-time PCR assays according to the Centers for Disease Control and Prevention (CDC) protocols. In cases where the influenza virus type was identified, complete hemagglutinin (HA) gene sequencing and the related phylogenetic analysis were conducted. The outbreak was caused by influenza A(H3N2): the attack rate was 83.3% in children aged 9–14 years, 84.6% in those aged 15–24 years, and 28.6% in adults ≥25 years. Phylogenetic analyses uncovered that A(H3N2) strains were closely related since they segregated in the same cluster, showing both a high mean nucleotide identity (100%), all belonging to the genetic sub-group 3C.2a1b.2a.2, as those mainly circulating into the general population in the same period. The fact that influenza outbreak strains as well as the community strains were genetically related to the seasonal vaccine strain suggests that if an influenza prevention by vaccination strategy had been implemented, a lower attack rate of A(H3N2) and ILI cases might have been achieved. [ABSTRACT FROM AUTHOR]
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- 2024
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31. Regulation of osteoclast differentiation and inflammatory signaling by TCF8 in periodontitis.
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Sun, Shiqun, Yan, Tongtong, Yang, Nan, Wu, Jian, and Liu, Zhihui
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BIOLOGICAL models , *BONE resorption , *IN vitro studies , *NF-kappa B , *CARRIER proteins , *PHOSPHORYLATION , *BONE growth , *COMPUTED tomography , *RNA virus infections , *CELLULAR signal transduction , *IN vivo studies , *FLUORESCENT antibody technique , *DESCRIPTIVE statistics , *RATS , *RNA , *OSTEOCLASTS , *ANIMAL experimentation , *LIPOPOLYSACCHARIDES , *INFLAMMATION , *CELL differentiation , *GRAM-negative anaerobic bacteria , *MOLECULAR biology , *COMPARATIVE studies , *PERIODONTITIS , *MEMBRANE proteins - Abstract
Objectives: The aim of this study was to explore the potential role of zinc‐finger homeodomain transcription factor (TCF8) in osteoclastogenesis and inflammation during periodontitis. Materials and Methods: Rats with periodontitis were induced via Porphyromonas gingivalis‐lipopolysaccharide (Pg‐LPS) injection. The recombinant lentivirus delivering short hairpin RNA (shRNA) against TCF8 was used to downregulate TCF8 in vivo. Alveolar bone loss in rats was determined by micro‐computed tomography (Micro‐CT). Typical pathological changes, periodontal tissue inflammation, and osteoclastogenesis were evaluated via histological analyses. The RAW264.7‐derived osteoclasts were induced by RANKL stimulation. TCF8 downregulation in vitro was achieved by lentivirus infection. The osteoclast differentiation and inflammatory signaling in RANKL‐induced cells were measured via immunofluorescence methods and molecular biology approaches. Results: Porphyromonas gingivalis‐lipopolysaccharide induced rats exhibited overexpressed TCF8 in their periodontal tissues, while TCF8 knockdown attenuated the bone loss, tissue inflammation, and osteoclastogenesis in LPS‐induced rats. Besides, TCF8 silencing inhibited RANKL‐induced osteoclast differentiation in RAW264.7 cells, as evidenced by the reduced numbers of TRAP‐positive osteoclasts, less formation of F‐actin rings, and downregulated expressions of osteoclast‐specific markers. It also exerted an inhibitory effect on the NF‐κB signaling in RANKL‐induced cells via blocking NF‐κB p65 phosphorylation and nuclear translocation. Conclusions: TCF8 silencing inhibited alveolar bone loss, osteoclast differentiation, and inflammation in periodontitis. [ABSTRACT FROM AUTHOR]
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- 2024
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32. Age-Specific Resurgence in Invasive Pneumococcal Disease Incidence in the COVID-19 Pandemic Era and Its Association With Respiratory Virus and Pneumococcal Carriage Dynamics: A Time-Series Analysis.
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Rybak, Alexis, Assad, Zein, Levy, Corinne, Bonarcorsi, Stéphane, Béchet, Stéphane, Werner, Andreas, Wollner, Alain, Valtuille, Zaba, Kaguelidou, Florentia, Angoulvant, François, Cohen, Robert, Varon, Emmanuelle, and Ouldali, Naïm
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CARRIER state (Communicable diseases) , *RISK assessment , *URINARY tract infections , *POISSON distribution , *STATISTICAL models , *RESPIRATORY infections , *RESEARCH funding , *DATA analysis , *RNA virus infections , *HOSPITAL care , *AGE distribution , *TIME series analysis , *RESPIRATORY syncytial virus infections , *INFLUENZA , *DESCRIPTIVE statistics , *STAY-at-home orders , *DOSE-response relationship in biochemistry , *STATISTICS , *STREPTOCOCCAL diseases , *VIRUS diseases , *CONFIDENCE intervals , *PUBLIC health , *COVID-19 pandemic , *DISEASE incidence , *DNA virus diseases , *DISEASE risk factors , *CHILDREN - Abstract
Using multiple national surveillance systems, we found an increase in the incidence of invasive pneumococcal disease during after the relaxation of non-pharmaceutical interventions against COVID-19, which strongly varied by age. Age groups with higher incidence of respiratory syncytial virus and influenza also experienced higher increase in invasive pneumococcal disease incidence, with no change in pneumococcal carriage. [ABSTRACT FROM AUTHOR]
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- 2024
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33. Porcine reproductive and respiratory syndrome virus 2 hijacks CMA-mediated lipolysis through upregulation of small GTPase RAB18.
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Li, Guo-Li, Han, Ying-Qian, Su, Bing-Qian, Yu, Hai-Shen, Zhang, Shuang, Yang, Guo-Yu, Wang, Jiang, Liu, Fang, Ming, Sheng-Li, and Chu, Bei-Bei
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PORCINE reproductive & respiratory syndrome , *RNA virus infections , *GUANOSINE triphosphatase , *HEAT shock proteins , *MEMBRANE proteins , *GENETIC variation , *LIPOLYSIS - Abstract
RAB GTPases (RABs) control intracellular membrane trafficking with high precision. In the present study, we carried out a short hairpin RNA (shRNA) screen focused on a library of 62 RABs during infection with porcine reproductive and respiratory syndrome virus 2 (PRRSV-2), a member of the family Arteriviridae. We found that 13 RABs negatively affect the yield of PRRSV-2 progeny virus, whereas 29 RABs have a positive impact on the yield of PRRSV-2 progeny virus. Further analysis revealed that PRRSV-2 infection transcriptionally regulated RAB18 through RIG-I/MAVS-mediated canonical NF-κB activation. Disrupting RAB18 expression led to the accumulation of lipid droplets (LDs), impaired LDs catabolism, and flawed viral replication and assembly. We also discovered that PRRSV-2 co-opts chaperone-mediated autophagy (CMA) for lipolysis via RAB18, as indicated by the enhanced associations between RAB18 and perlipin 2 (PLIN2), CMA-specific lysosomal associated membrane protein 2A (LAMP2A), and heat shock protein family A (Hsp70) member 8 (HSPA8/HSC70) during PRRSV-2 infection. Knockdown of HSPA8 and LAMP2A impacted on the yield of PRRSV-2 progeny virus, implying that the virus utilizes RAB18 to promote CMA-mediated lipolysis. Importantly, we determined that the C-terminal domain (CTD) of HSPA8 could bind to the switch II domain of RAB18, and the CTD of PLIN2 was capable of associating with HSPA8, suggesting that HSPA8 facilitates the interaction between RAB18 and PLIN2 in the CMA process. In summary, our findings elucidate how PRRSV-2 hijacks CMA-mediated lipid metabolism through innate immune activation to enhance the yield of progeny virus, offering novel insights for the development of anti-PRRSV-2 treatments. Author summary: Two species of arteriviruses, a family of RNA viruses, can cause severe reproductive disorders and respiratory diseases in infected piglets that result in significant economic losses in the swine industry. The respective viruses conventionally known as PRRSV-1 and PRRSV-2 exhibit high genetic variability and immune evasion capabilities, which complicate the development of effective vaccines and control measures. In this study, we have described a unique mechanism by which PRRSV-2 infection stimulates RAB18 expression through RIG-I/MAVS-mediated canonical NF-κB activation. RAB18 then recruits HSPA8 and PLIN2 for CMA-mediated degradation and subsequent lipolysis, facilitating viral replication and assembly. Our study provides new insights into the interplay between innate immunity, RAB18, and the CMA-mediated lipophagy pathway during RNA virus infection. [ABSTRACT FROM AUTHOR]
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- 2024
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34. Bat STING drives IFN-beta production in anti-RNA virus innate immune response.
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Feiyu Fu, Qi Shao, Jianjian Zhang, Jie Wang, Zhaofei Wang, Jingjiao Ma, Yaxian Yan, Jianhe Sun, and Yuqiang Cheng
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RNA virus infections ,GREEN fluorescent protein ,GENE expression ,VESICULAR stomatitis ,IMMUNE response ,INTERFERON receptors - Abstract
The ability of stimulator of interferon genes (STING) to activate interferon (IFN) responses during RNA virus infection has been demonstrated in different mammalian cells. Despite being the host of numerous RNA viruses, the role of STING in bats during RNA virus infection has not been elucidated. In this study, we identified and cloned the STING gene of the Brazilian free-tailed bat Tadarida brasiliensis (T. brasiliensis) and tested its ability to induce IFN-ß by overexpressing and knocking down bat STING (BatSTING) in T. brasiliensis 1 lung (TB1 Lu) cells. In addition, we used green fluorescent protein (GFP)-labeled vesicular stomatitis virus (VSV) VSV-GFP as a model to detect the antiviral activity of BatSTING. The results showed that overexpression of STING in TB1 Lu cells stimulated by cGAS significantly inhibited RNA virus replication, and the antiviral activities were associated with its ability to regulate basal expression of IFN-ß and some IFN stimulated genes (ISGs). We also found that BatSTING was able to be activated after stimulation by diverse RNA viruses. The results of TB1 Lu cells with STING deficiency showed that knockdown of BatSTING severely hindered the IFN-ß response triggered by VSV-GFP. Based on this, we confirm that BatSTING is required to induce IFN-ß expression during RNA virus infection. In conclusion, our experimental data clearly show that STING in bat hosts plays an irreplaceable role in mediating IFN-ß responses and anti-RNA virus infection. [ABSTRACT FROM AUTHOR]
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- 2024
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35. Development of a Novel Plasmid-based Eukaryotic Model to Investigate Crimean-Congo Hemorrhagic Fever Virus.
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ÇETİN, Nesibe Selma GÜLER, BAKANGİL, Özlem, YAZICI, Merve KALKAN, KESKİN, Sercan, and DOYMAZ, Mehmet Ziya
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HEMORRHAGIC fever , *VIRUS-like particles , *VIRAL proteins , *GENE expression , *GENE transfection , *WESTERN immunoblotting - Abstract
Objective: Crimean-Congo Hemorrhagic Fever (CCHF) is a severe tick-borne viral disease, caused by the Crimean-Congo Hemorrhagic Fever virus (CCHFV). The global expansion of CCHF and high mortality rates underline the critical need for research and development of effective treatments and vaccines. However, the high risk of transmission and requirement for highcontainment facilities hinder investigations involving live virus. In this study, we aimed to address these challenges by employing a plasmid-based virus-like particle (VLP) system and a minigenome model to investigate the biology and immunology of CCHFV. Methods: The plasmids encoding CCHFV structural genes of CCHFV were transfected into Huh-7 cells. Viral protein expression was confirmed using fluorescence imaging, immunological and molecular methods. A minigenome system was developed, eliminating the need for T7 polymerase, T7-expressing cellular lines, or viral ribonuclear protein complexes, allowing autonomous virus replication without a helper virus or transfections using plasmids in trans. Results: Fluorescence microscopy showed successful production of NP-EGFP and GC-EGFP proteins with various subcellular localizations. Western blot analysis demonstrated the presence of pre-Gc, Gc, pre-Gn, Gn, and Np proteins in cell lysates and supernatants. ELISA analysis suggested that transfection of Np alone, in combination with Gc, or all three proteins might cause distinct VLP formations. Huh-7 cells successfully expressed reporter genes after transfection of minigenome RNA transcripts. Conclusion: The study advances CCHFV research by using novel tools for virus biology and immunology. The findings may provide new avenues for research that promise better public health preparation against this neglected viral disease. [ABSTRACT FROM AUTHOR]
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- 2024
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36. Pharmacogenomic Studies of Antiviral Drug Favipiravir.
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Shumyantseva, Victoria V., Bulko, Tatiana V., Chistov, Alexey A., Kolesanova, Ekaterina F., and Agafonova, Lyubov E.
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ADENINE , *ANTIVIRAL agents , *TITANIUM oxide nanotubes , *RNA virus infections , *GUANINE , *ELECTROCHEMICAL analysis , *INTERCALATION reactions - Abstract
In this work, we conducted a study of the interaction between DNA and favipiravir (FAV). This chemotherapeutic compound is an antiviral drug for the treatment of COVID-19 and other infections caused by RNA viruses. This paper examines the electroanalytical characteristics of FAV. The determined concentrations correspond to therapeutically significant ones in the range of 50–500 µM (R2 = 0.943). We have shown that FAV can be electro-oxidized around the potential of +0.96 V ÷ +0.98 V (vs. Ag/AgCl). A mechanism for electrochemical oxidation of FAV was proposed. The effect of the drug on DNA was recorded as changes in the intensity of electrochemical oxidation of heterocyclic nucleobases (guanine, adenine and thymine) using screen-printed graphite electrodes modified with single-walled carbon nanotubes and titanium oxide nanoparticles. In this work, the binding constants (Kb) of FAV/dsDNA complexes for guanine, adenine and thymine were calculated. The values of the DNA-mediated electrochemical decline coefficient were calculated as the ratio of the intensity of signals for the electrochemical oxidation of guanine, adenine and thymine in the presence of FAV to the intensity of signals for the electro-oxidation of these bases without drug (S, %). Based on the analysis of electrochemical parameters, values of binding constants and spectral data, intercalation was proposed as the principal mechanism of the antiviral drug FAV interaction with DNA. The interaction with calf thymus DNA also confirmed the intercalation mechanism. However, an additional mode of interaction, such as a damage effect together with electrostatic interactions, was revealed in a prolonged exposure of DNA to FAV. [ABSTRACT FROM AUTHOR]
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- 2024
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37. Activated sludge and UV-C254 for Sapovirus, Aichivirus, Astrovirus, and Adenovirus processing.
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Ibrahim, Chourouk, Hammami, Salah, khelifi, Nesserine, Pothier, Pierre, and Hassen, Abdennaceur
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DIARRHEA , *RESEARCH funding , *RNA virus infections , *ADENOVIRUSES , *REVERSE transcriptase polymerase chain reaction , *RNA viruses , *ENTEROVIRUSES , *STERILIZATION (Disinfection) , *WATER supply , *WATER pollution , *POLLUTION , *GASTROENTERITIS , *MINERALS , *DNA virus diseases , *SEWAGE - Abstract
In this study, the detection rates of four enteric viruses, Human Astrovirus (HAstVs), Aichivirus (AiVs), Human Adenovirus (HAdVs), and Sapovirus (SaVs) are carried out to assess the virological quality of the treated wastewater. A total of 140 samples was collected from wastewater treatment plant WWTP of Tunis-City. Real-time RT-PCR and conventional RT-PCR results showed high frequencies of detection of the four enteric viruses investigated at the entry and exit of the biological activated sludge procedure and a significant reduction in viral titers after tertiary treatment with UV-C254 irradiation. These results revealed the ineffectiveness of the biological activated sludge treatment in removing viruses and the poor quality of the treated wastewater intended for recycling, agricultural reuse, and safe discharge into the natural environment. The UV-C254 irradiation, selected while considering the non-release of known disinfection by-products because of eventual reactions with the large organic and mineral load commonly present in the wastewater. [ABSTRACT FROM AUTHOR]
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- 2024
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38. Reply to Qu et al., "Quasispecies are constantly selected through virus-encoded intracellular reproductive population bottlenecking".
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Domingo, Esteban, Martínez-González, Brenda, García-Crespo, Carlos, Somovilla, Pilar, Isabel de Ávila, Ana, Soria, María Eugenia, Durán-Pastor, Antoni, and Perales, Celia
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COMPLEMENTATION (Genetics) , *BACTERIOPHAGES , *VIRUS diseases , *RECOMBINANT viruses , *RNA virus infections , *INFLUENZA viruses , *INFLUENZA A virus - Abstract
This document is a response to a letter discussing the concept of quasispecies in viruses. The authors of the response disagree with the assertion that viral populations become bottlenecked upon entering a cell, eliminating interactions between mutant genomes. They provide examples of coexistence and interactions between mutant and recombinant viral genomes within infected cells, which have been observed in various studies. The authors argue that evidence of intra-mutant spectrum interactions within cells is overwhelming and necessary to explain the origin of recombinant and reassortant viruses. The document also discusses the methodology of single-cell ultra-deep sequencing RNA analysis and its potential to detect new mutations in viral RNA replication. The authors are affiliated with research institutions in Madrid, Spain, and the study was funded by several organizations. [Extracted from the article]
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- 2024
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- View/download PDF
39. Severe fever with thrombocytopenia syndrome: one case report.
- Author
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XU Jin-mei, LIU Bing-jian, GUAN Hong-zhi, SHAN Ping, CHEN Guo-hua, and MEI Jun-hua
- Subjects
RNA virus infections ,GENETIC techniques ,TICK-borne diseases - Published
- 2024
- Full Text
- View/download PDF
40. In the Literature.
- Author
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Deresinski, Stanley C
- Subjects
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COMMUNICABLE diseases , *PHENOMENOLOGICAL biology , *HEALTH , *RNA virus infections , *IMMUNOCOMPROMISED patients , *INFORMATION resources , *AUTOINFLAMMATORY diseases , *BIOCHEMISTRY , *KLEBSIELLA infections , *PEPTIDES , *MEDICAL literature , *GENETIC mutation , *CEFOXITIN , *DISEASE complications - Abstract
The article focuses on comparing cefoxitin and carbapenems as treatments for bacteremia caused by extended-spectrum β-lactamase (ESBL)–producing Klebsiella pneumoniae. Topics include the retrospective analysis of treatment outcomes, the impact of treatment choice on clinical and microbiological success, and the potential for selection of resistant organisms.
- Published
- 2024
- Full Text
- View/download PDF
41. Anti-E alloimmunization from a platelet apheresis transfusion in a 22-month-old male with acute myeloid leukemia.
- Author
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Burks, Martin, Warren, Christina S, Lightfoot, Thomas, and Fadeyi, Emmanuel A
- Subjects
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RED blood cell transfusion , *COOMBS' test , *BIOPSY , *FLOW cytometry , *BLOOD group incompatibility , *ERYTHROCYTES , *DOWN syndrome , *RESPIRATORY infections , *BONE marrow , *IMMUNOGLOBULINS , *PURPURA (Pathology) , *ADENOVIRUSES , *RNA virus infections , *FATIGUE (Physiology) , *HOSPITAL care , *BLOOD platelet transfusion , *FEVER , *BLOOD groups , *CENTRAL venous catheterization , *THROMBOCYTOPENIA , *ANTIGENS , *BODY temperature , *CANCER chemotherapy , *CYTARABINE , *PATHOLOGICAL laboratories , *COUGH , *GENOTYPES , *DAUNOMYCIN , *DEXAMETHASONE ,BONE marrow examination - Abstract
RhD alloimmunization from platelet transfusions have been documented in the literature. However, non-RhD platelet alloimmunization is much less frequent and the risk for non-RhD alloimmunization from platelets is thought to be extremely low and most associated with buffy coat pooled platelets. A 22-month-old male with acute myeloid leukemia received 99 mL apheresis platelets for thrombocytopenia. Three months later, an antibody screen, the direct antiglobulin test (DAT), and red blood cell (RBC) genotype were sent for laboratory evaluation. The antibody screen was positive, with anti-E identified. The DAT was negative and the RBC genotype of the patient was predicted to be negative for the E antigen whereas the platelet donor was predicted to be positive for E antigen. There is a risk of alloimmunization of non-RhD antigen from platelet pheresis transfusion even in a patient less than 2 years old. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
42. South Asia's Strategic Readiness Amidst Worsening Nipah Virus Threats: Current Situation and Imperatives.
- Author
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Singh, Ajeet, Fatima, Laveeza, Shaikh, Bisma, and Khatri, Govinda
- Subjects
PUBLIC health surveillance ,HEALTH literacy ,RNA virus infections ,PANDEMIC preparedness ,VACCINATION coverage ,ZOONOSES ,MEDICAL screening ,EARLY diagnosis ,COALITIONS - Published
- 2024
- Full Text
- View/download PDF
43. Ad26.ZEBOV, MVA-BN-Filo Vaccination in Children and Adults Previously Vaccinated With Control in the EBOVAC-Salone Study
- Author
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University of Sierra Leone and Janssen Vaccines & Prevention B.V.
- Published
- 2023
44. Self-Test Strategies and Linkage Incentives to Improve ART and PrEP Uptake in Men
- Author
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University of Pennsylvania, Impact Research & Development Organization, National Institute of Mental Health (NIMH), Duke University, and Kenya Medical Research Institute
- Published
- 2023
45. Efficacy, Safety, and Immunogenicity of a Plant-Derived Quadrivalent Virus-Like Particles (VLPs) Influenza Vaccine in Adults
- Published
- 2023
46. Lot-to-lot Consistency of a Plant-Derived Quadrivalent Virus-Like Particles Influenza Vaccine in Healthy Adults
- Published
- 2023
47. A Study to Evaluate Safety and Immunogenicity of One or Two Booster Vaccinations With H5N6 Influenza Vaccine in Adults Primed With H5N1 Influenza Vaccine or Unprimed
- Published
- 2023
48. Western equine encephalitis: geographical patterns and range expansion of an emerging arbovirus disease in the Americas.
- Author
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Kim, Jisoo, Macias, Jessica, Bo Young Yoon, Charette, Margot, Areda, Betel, Ravikumar, Rajkrishna, de Fritas, Diego, Alfonso, Adriana, Anchen, Mariela, Martín, Rosario San, Lebrero, Cecilia González, Giovacchini, Carlos, Fernandez, Gabriela, Maffey, Lucia, Marcos, Andrea, and Almiróna, Maria
- Subjects
- *
DISEASE vectors , *RNA virus infections , *MOSQUITO vectors , *POPULATION geography , *EASTERN equine encephalomyelitis , *FEVER , *RNA viruses , *DISEASES , *VIRAL encephalitis , *ARBOVIRUSES , *INFECTIOUS disease transmission , *ANIMAL diseases , *VERTEBRATES - Abstract
The article offers information on Western equine encephalitis virus (WEEV), a mosquito-borne arbovirus that circulates enzootically among birds but can be transmitted indirectly from vertebrate animals to humans through arthropod vectors in a complex life cycle. Topics discussed include epidemiology of WEEV infection in the Americas, spatial and temporal distribution of WEEV, and other emerging vector-borne viruses reported in 2023 in the Americas.
- Published
- 2024
49. Efficacy of a Plant-derived Quadrivalent Virus-like Particle (VLP) Vaccine in the Elderly
- Published
- 2023
50. Enhancing Innate Anti-Viral Resistance Through A Community-Based Intervention - Generation Xchange (GenX)
- Author
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National Institute on Aging (NIA) and Steve Cole, Ph.D., Professor of Medicine and Psychiatry & Biobehavioral Sciences
- Published
- 2023
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