70 results on '"Ren-Rong Tian"'
Search Results
2. Increased cAMP-PKA signaling pathway activation is involved in up-regulation of CTLA-4 expression in CD4+ T cells in acute SIVmac239-infected Chinese rhesus macaques
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Ren-Rong Tian, Ben-Bo Liu, Ming-Liang Zhao, Yu-Jun Cai, and Yong-Tang Zheng
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HIV ,CTLA-4 ,cAMP-PKA signaling pathway ,Non-human primate models ,Microbiology ,QR1-502 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Human immunodeficiency virus-1 (HIV-1) infection can cause chronic activation, exhaustion, and anergy of the immune system. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is an immune checkpoint molecule, which plays an important role in immune homeostasis and disease. CTLA-4 expression is elevated in HIV-1-infected patients and is associated with disease progression. However, the mechanism controlling expression of CTLA-4 in HIV-1 infection is poorly characterized. In this study, we used a SIV-infected Chinese rhesus macaque (ChRM) model to explore CTLA-4 expression in SIV infection. Results showed that SIV infection significantly increased CTLA-4 expression in all T cell subsets, especially central memory T cells. CTLA-4+CD4+ T cell frequency was significantly associated with disease progression markers. Activation of the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway regulated CTLA-4 expression in CD4+T cells, as confirmed by stimulation with dibutyryl cyclic adenosine monophosphate, forskolin, and 3-isobutyl-1-methylxanthine, and inhibition with H-89 ex vivo. Simultaneously, cAMP concentration in PBMCs and PKA activity in both PBMCs and CD4+ T cells were increased in acute SIV-infected ChRMs, accompanied by an increase in adenylate cyclase 6 expression and a decrease in cAMP-phosphodiesterase 3A (PDE3A), PDE4B, and PDE5A expression in PBMCs. In addition, selective inhibition of PDE4B and PDE5A activity enhanced CTLA-4 expression in CD4+ T cells. These results suggest that SIV infection alters cAMP metabolism and increases cAMP-PKA signaling pathway activation, which up-regulates the expression of CTLA-4 in acute SIVmac239-infected ChRMs. Thus, regulation of the cAMP-PKA signaling pathway may be a potential strategy for the restoration of T cell function and therapy for AIDS.
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- 2024
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3. Novel Circovirus in Blood from Intravenous Drug Users, Yunnan, China
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Yanpeng Li, Peng Zhang, Mei Ye, Ren-Rong Tian, Na Li, Le Cao, Yingying Ma, Feng-Liang Liu, Yong-Tang Zheng, and Chiyu Zhang
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circovirus ,IDU ,intravenous drug users ,viruses ,viral metagenomics ,emerging virus ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
We identified a novel circovirus (human-associated circovirus 2 [HuCV2]) from the blood of 2 intravenous drug users in China who were infected with HIV-1, hepatitis C virus, or both. HuCV2 is most closely related to porcine circovirus 3. Our findings underscore the risk for HuCV2 and other emerging viruses among this population.
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- 2023
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4. Preventive and therapeutic benefits of nelfinavir in rhesus macaques and human beings infected with SARS-CoV-2
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Zhijian Xu, Danrong Shi, Jian-Bao Han, Yun Ling, Xiangrui Jiang, Xiangyun Lu, Chuan Li, Likun Gong, Guangbo Ge, Yani Zhang, Yi Zang, Tian-Zhang Song, Xiao-Li Feng, Ren-Rong Tian, Jia Ji, Miaojin Zhu, Nanping Wu, Chunhui Wu, Zhen Wang, Yechun Xu, Cheng Peng, Min Zheng, Junling Yang, Feifei Du, Junliang Wu, Peipei Wang, Jingshan Shen, Jianliang Zhang, Yong-Tang Zheng, Hangping Yao, and Weiliang Zhu
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Medicine ,Biology (General) ,QH301-705.5 - Abstract
Abstract Effective drugs with broad spectrum safety profile to all people are highly expected to combat COVID-19 caused by SARS-CoV-2. Here we report that nelfinavir, an FDA approved drug for the treatment of HIV infection, is effective against SARS-CoV-2 and COVID-19. Preincubation of nelfinavir could inhibit the activity of the main protease of the SARS-CoV-2 (IC50 = 8.26 μM), while its antiviral activity in Vero E6 cells against a clinical isolate of SARS-CoV-2 was determined to be 2.93 μM (EC50). In comparison with vehicle-treated animals, rhesus macaque prophylactically treated with nelfinavir had significantly lower temperature and significantly reduced virus loads in the nasal and anal swabs of the animals. At necropsy, nelfinavir-treated animals had a significant reduction of the viral replication in the lungs by nearly three orders of magnitude. A prospective clinic study with 37 enrolled treatment-naive patients at Shanghai Public Health Clinical Center, which were randomized (1:1) to nelfinavir and control groups, showed that the nelfinavir treatment could shorten the duration of viral shedding by 5.5 days (9.0 vs. 14.5 days, P = 0.055) and the duration of fever time by 3.8 days (2.8 vs. 6.6 days, P = 0.014) in mild/moderate COVID-19 patients. The antiviral efficiency and clinical benefits in rhesus macaque model and in COVID-19 patients, together with its well-established good safety profile in almost all ages and during pregnancy, indicated that nelfinavir is a highly promising medication with the potential of preventative effect for the treatment of COVID-19.
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- 2023
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5. Severe fever with thrombocytopenia syndrome virus induces platelet activation and apoptosis via a reactive oxygen species-dependent pathway
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Yi-Hui Li, Xue-Hui Wang, Wen-Wu Huang, Ren-Rong Tian, Wei Pang, and Yong-Tang Zheng
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SFTSV ,Thrombocytopenia ,Platelet activation ,Platelet apoptosis ,Antioxidants ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by the SFTS virus (SFTSV) and with a high fatality rate. Thrombocytopenia is a major clinical manifestation observed in SFTS patients, but the underlying mechanism remains largely unclear. Here, we explored the effects of SFTSV infection on platelet function in vivo in severely infected SFTSV IFNar−/− mice and on mouse and human platelet function in vitro. Results showed that SFTSV-induced platelet clearance acceleration may be the main reason for thrombocytopenia. SFTSV-potentiated platelet activation and apoptosis were also observed in infected mice. Further investigation showed that SFTSV infection induced platelet reactive oxygen species (ROS) production and mitochondrial dysfunction. In vitro experiments revealed that administration of SFTSV or SFTSV glycoprotein (Gn) increased activation, apoptosis, ROS production, and mitochondrial dysfunction in separated mouse platelets, which could be effectively ameliorated by the application of antioxidants (NAC (N-acetyl-l-cysteine), SKQ1 (10-(6′-plastoquinonyl) decyltriphenylphosphonium) and resveratrol). In vivo experiments showed that the antioxidants partially rescued SFTSV infection-induced thrombocytopenia by improving excessive ROS production and mitochondrial dysfunction and down-regulating platelet apoptosis and activation. Furthermore, while SFTSV and Gn directly potentiated human platelet activation, it was completely abolished by antioxidants. This study revealed that SFTSV and Gn can directly trigger platelet activation and apoptosis in an ROS-MAPK-dependent manner, which may contribute to thrombocytopenia and hemorrhage during infection, but can be abolished by antioxidants.
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- 2023
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6. Pro-inflammatory microenvironment and systemic accumulation of CXCR3+ cell exacerbate lung pathology of old rhesus macaques infected with SARS-CoV-2
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Hong-Yi Zheng, Xiao-Yan He, Wei Li, Tian-Zhang Song, Jian-Bao Han, Xiang Yang, Feng-Liang Liu, Rong-Hua Luo, Ren-Rong Tian, Xiao-Li Feng, Yu-Hua Ma, Chao Liu, Ming-Hua Li, and Yong-Tang Zheng
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Medicine ,Biology (General) ,QH301-705.5 - Abstract
Abstract Understanding the pathological features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in an animal model is crucial for the treatment of coronavirus disease 2019 (COVID-19). Here, we compared immunopathological changes in young and old rhesus macaques (RMs) before and after SARS-CoV-2 infection at the tissue level. Quantitative analysis of multiplex immunofluorescence staining images of formalin-fixed paraffin-embedded (FFPE) sections showed that SARS-CoV-2 infection specifically induced elevated levels of apoptosis, autophagy, and nuclear factor kappa-B (NF-κB) activation of angiotensin-converting enzyme 2 (ACE2)+ cells, and increased interferon α (IFN-α)- and interleukin 6 (IL-6)-secreting cells and C-X-C motif chemokine receptor 3 (CXCR3)+ cells in lung tissue of old RMs. This pathological pattern, which may be related to the age-related pro-inflammatory microenvironment in both lungs and spleens, was significantly correlated with the systemic accumulation of CXCR3+ cells in lungs, spleens, and peripheral blood. Furthermore, the ratio of CXCR3+ to T-box protein expression in T cell (T-bet)+ (CXCR3+/T-bet+ ratio) in CD8+ cells may be used as a predictor of severe COVID-19. These findings uncovered the impact of aging on the immunopathology of early SARS-CoV-2 infection and demonstrated the potential application of CXCR3+ cells in predicting severe COVID-19.
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- 2021
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7. Longitudinal transcriptome analyses show robust T cell immunity during recovery from COVID-19
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Hong-Yi Zheng, Min Xu, Cui-Xian Yang, Ren-Rong Tian, Mi Zhang, Jian-Jian Li, Xi-Cheng Wang, Zhao-Li Ding, Gui-Mei Li, Xiao-Lu Li, Yu-Qi He, Xing-Qi Dong, Yong-Gang Yao, and Yong-Tang Zheng
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Medicine ,Biology (General) ,QH301-705.5 - Abstract
Abstract Understanding the processes of immune regulation in patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial for improving treatment. Here, we performed longitudinal whole-transcriptome RNA sequencing on peripheral blood mononuclear cell (PBMC) samples from 18 patients with coronavirus disease 2019 (COVID-19) during their treatment, convalescence, and rehabilitation. After analyzing the regulatory networks of differentially expressed messenger RNAs (mRNAs), microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) between the different clinical stages, we found that humoral immunity and type I interferon response were significantly downregulated, while robust T-cell activation and differentiation at the whole transcriptome level constituted the main events that occurred during recovery from COVID-19. The formation of this T cell immune response might be driven by the activation of activating protein-1 (AP-1) related signaling pathway and was weakly affected by other clinical features. These findings uncovered the dynamic pattern of immune responses and indicated the key role of T cell immunity in the creation of immune protection against this disease.
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- 2020
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8. Glucose Metabolism Disorder Induces Spermatogenic Dysfunction in Northern Pig-Tailed Macaques (Macaca leonina) With Long-Term SIVmac239 Infection
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Tian-Zhang Song, Ming-Xu Zhang, Han-Dan Zhang, Xue-Hui Wang, Wei Pang, Ren-Rong Tian, and Yong-Tang Zheng
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spermatogenic dysfunction ,glucose metabolism ,Macaca leonina ,northern pig-tailed macaques ,SIVmac239 ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Although spermatogenic dysfunction is widely found in patients with human immunodeficiency virus (HIV), the underlying reasons remain unclear. Thus far, potential hypotheses involving viral reservoirs, testicular inflammation, hormone imbalance, and cachexia show inconsistent correlation with spermatogenic dysfunction. Here, northern pig-tailed macaques (NPMs) exhibited marked spermatogenic dysfunction after long-term infection with simian immunodeficiency virus (SIVmac239), with significant decreases in Johnsen scores, differentiated spermatogonial stem cells, and testicular proliferating cells. The above hypotheses were also evaluated. Results showed no differences between SIV− and SIV+ NPMs, except for an increase in follicle stimulating hormone (FSH) during SIV infection, which had no direct effect on the testes. However, long-term SIVmac239 infection undermined pancreatic islet β cell function, partly represented by significant reductions in cellular counts and autophagy levels. Pancreatic islet β cell dysfunction led to glucose metabolism disorder at the whole-body level, which inhibited lactate production by Sertoli cells in testicular tissue. As lactate is the main energy substrate for developing germ cells, its decrease was strongly correlated with spermatogenic dysfunction. Therefore, glucose metabolism disorder appears to be a primary cause of spermatogenic dysfunction in NPMs with long-term SIVmac239 infection.
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- 2021
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9. Transcription Factor ZNF683 Inhibits SIV/HIV Replication through Regulating IFNγ Secretion of CD8+ T Cells
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Ying Lu, Ming-Xu Zhang, Wei Pang, Tian-Zhang Song, Hong-Yi Zheng, Ren-Rong Tian, and Yong-Tang Zheng
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lung ,SIVmac239 ,slow progressors ,rapid progressors ,northern pig-tailed macaques ,ZNF683 ,Microbiology ,QR1-502 - Abstract
Pulmonary microbial invasion frequently occurs during AIDS progression in HIV patients. Inflammatory cytokines and other immunoregulatory factors play important roles in this process. We previously established an AIDS model of SIVmac239 infection in northern pig-tailed macaques (NPMs), which were divided into rapid progressor (RP) and slow progressor (SP) groups according to their AIDS progression rates. In this study, we performed 16S rDNA and transcriptome sequencing of the lungs to reveal the molecular mechanism underlying the difference in progression rate between the RPs and SPs. We found that microbial invasion in the RP group was distinct from that in the SP group, showing marker flora of the Family XI, Enterococcus and Ezakiella, and more Lactobacilli. Through pulmonary transcriptome analysis, we found that the transcription factor ZNF683 had higher expression in the SP group than in the RP group. In subsequent functional experiments, we found that ZNF683 increased the proliferation and IFNγ secretion ability of CD8+ T cells, thus decreasing SIV or HIV replication, which may be related to AIDS progression in SIVmac239-infected NPMs. This study helps elucidate the various complexities of disease progression in HIV-1-infected individuals.
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- 2022
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10. Bromodomain and Extra-Terminal Inhibitor BMS-986158 Reverses Latent HIV-1 Infection In Vitro and Ex Vivo by Increasing CDK9 Phosphorylation and Recruitment
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Xu-Sheng Huang, Ren-Rong Tian, Meng-Di Ma, Rong-Hua Luo, Liu-Meng Yang, Guang-Hui Peng, Mi Zhang, Xing-Qi Dong, and Yong-Tang Zheng
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HIV-1 ,BET ,BMS-986158 ,latency reversing agent ,latent reservoir ,Medicine ,Pharmacy and materia medica ,RS1-441 - Abstract
Latent reservoir persistence remains a major obstacle for curing human immunodeficiency virus type 1 (HIV-1) infection. Thus, strategies for the elimination of latent HIV-1 are urgently needed. As a bromodomain and extra-terminal (BET) inhibitor, BMS-986158 has been used in clinical trials for advanced solid tumors and hematological malignancies. Here, we found that BMS-986158 reactivated latent HIV-1 in three types of HIV-1 latency cells in vitro, and in combination antiretroviral therapy (cART)-treated patient-derived peripheral blood mononuclear cells ex vivo, without influencing global immune cell activation. BMS-986158 reactivated latent HIV-1 by increasing phosphorylation of CDK9 at Thr186 and promoting recruitment of CDK9 and RNA polymerase II to the HIV-1 long terminal repeat in J-Lat cells. Furthermore, BMS-986158 exerted strong synergism in reactivating latent HIV-1 when combined with prostratin and vorinostat and enhanced the antiviral activity of anti-HIV-1 drugs. Finally, BMS-986158 showed antiviral activity in an HIV-1 acute infection model, possibly by arresting the cell cycle in infected cells. Thus, these results suggest that BMS-986158 is a potential candidate for AIDS/HIV-1 therapy.
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- 2022
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11. Accelerated disease progression and robust innate host response in aged SIVmac239-infected Chinese rhesus macaques is associated with enhanced immunosenescence
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Hong-Yi Zheng, Ming-Xu Zhang, Min Chen, Jin Jiang, Jia-Hao Song, Xiao-Dong Lian, Ren-Rong Tian, Xiao-Liang Zhang, Lin-Tao Zhang, Wei Pang, Gao-Hong Zhang, and Yong-Tang Zheng
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Medicine ,Science - Abstract
Abstract The elderly population infected with HIV-1 is often characterized by the rapid AIDS progression and poor treatment outcome, possibly because of immunosenescence resulting from both HIV infection and aging. However, this hypothesis remains to be fully tested. Here, we studied 6 young and 12 old Chinese rhesus macaques (ChRM) over the course of three months after simian immunodeficiency virus (SIV) SIVmac239 infection. Old ChRM showed a higher risk of accelerated AIDS development than did young macaques, owing to rapidly elevated plasma viral loads and decreased levels of CD4+ T cells. The low frequency of naïve CD4+ T cells before infection was strongly predictive of an increased disease progression, whereas the severe depletion of CD4+ T cells and the rapid proliferation of naïve lymphocytes accelerated the exhaustion of naïve lymphocytes in old ChRM. Moreover, in old ChRM, a robust innate host response with defective regulation was associated with a compensation for naïve T cell depletion and a high level of immune activation. Therefore, we suggest that immunosenescence plays an important role in the accelerated AIDS progression in elderly individuals and that SIV-infected old ChRM may be a favorable model for studying AIDS pathogenesis and researching therapies for elderly AIDS patients.
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- 2017
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12. Lipopolysaccharide Increases Immune Activation and Alters T Cell Homeostasis in SHIVB’WHU Chronically Infected Chinese Rhesus Macaque
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Gao-Hong Zhang, Run-Dong Wu, Hong-Yi Zheng, Xiao-Liang Zhang, Ming-Xu Zhang, Ren-Rong Tian, Guang-Ming Liu, Wei Pang, and Yong-Tang Zheng
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Immunologic diseases. Allergy ,RC581-607 - Abstract
Immune activation plays a significant role in the disease progression of HIV. Microbial products, especially bacterial lipopolysaccharide (LPS), contribute to immune activation. Increasing evidence indicates that T lymphocyte homeostasis disruptions are associated with immune activation. However, the mechanism by which LPS affects disruption of immune response is still not fully understood. Chronically SHIVB’WHU-infected Chinese rhesus macaques received 50 μg/kg body weight LPS in this study. LPS administration affected the virus/host equilibrium by elevating the levels of viral replication and activating T lymphocytes. LPS induced upregulation of CD8+ naïve T cells and downregulated the number of CD4+ and CD8+ T effector memory cells. The downregulated effector memory cells are associated with a lower frequency of monofunctional and polyfunctional cells, and an upregulated programmed cell death-1 (PD-1) expression on CD4+ and CD8+ T cells was observed in monkeys after LPS stimulation. Our data provide new insights into the function of LPS in the immune activation in SHIV/HIV infection.
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- 2015
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13. Identification of novel mammalian viruses in tree shrews (Tupaia belangeri chinensis).
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Hong Zhou, Ren-Rong Tian, Xiu-Rong Wang, Jin-Xuan Yang, Yun-Xiao Wang, Ming-Liang Zhao, Xu-Dong Zhang, Yu-Hua Ma, Long-Bao Lv, Holmes, Edward C., Yong-Tang Zheng, and Wei-Feng Shi
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SHREWS ,REOVIRUSES ,ROTAVIRUSES ,VIRAL genomes ,TREES ,METABOLIC disorders ,COMMUNICABLE diseases - Abstract
The Chinese tree shrew (Tupaia belangeri chinensis), a member of the mammalian order Scandentia, exhibits considerable similarities with primates, including humans, in aspects of its nervous, immune, and metabolic systems. These similarities have established the tree shrew as a promising experimental model for biomedical research on cancer, infectious diseases, metabolic disorders, and mental health conditions. Herein, we used metatranscriptomic sequencing to analyze plasma, as well as oral and anal swab samples, from 105 healthy asymptomatic tree shrews to identify the presence of potential zoonotic viruses. In total, eight mammalian viruses with complete genomes were identified, belonging to six viral families, including Flaviviridae, Hepeviridae, Parvovirinae, Picornaviridae, Sedoreoviridae, and Spinareoviridae. Notably, the presence of rotavirus was recorded in tree shrews for the first time. Three viruses — hepacivirus 1, parvovirus, and picornavirus — exhibited low genetic similarity (<70%) with previously reported viruses at the whole-genome scale, indicating novelty. Conversely, three other viruses — hepacivirus 2, hepatovirus A and hepevirus — exhibited high similarity (>94%) to known viral strains. Phylogenetic analyses also revealed that the rotavirus and mammalian orthoreovirus identified in this study may be novel reassortants. These findings provide insights into the diverse viral spectrum present in captive Chinese tree shrews, highlighting the necessity for further research into their potential for crossspecies transmission. [ABSTRACT FROM AUTHOR]
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- 2024
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14. SARS-CoV-2 breakthrough infections following inactivated vaccine vaccination induce few neutralizing antibodies against the currently emerging Omicron XBB variants.
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Fan Shen, Chun Liang, Cui-Xian Yang, Ying Lu, An-Qi Li, Ying Duan, Mi Zhang, Ren-Rong Tian, Xing-Qi Dong, Yong-Tang Zheng, and Wei Pang
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SARS disease ,CORONAVIRUS diseases ,VACCINES ,CONVALESCENCE ,VIRUS diseases - Abstract
This article presents the findings of a study on breakthrough infections of the SARS-CoV-2 virus in individuals who had received inactivated vaccines. The study found that these breakthrough infections resulted in low levels of neutralizing antibodies against the emerging Omicron XBB variants. Even individuals who had received two or three doses of the vaccine had low levels of neutralizing antibodies against these variants. The study suggests that the effectiveness of immunoprotection in this population needs to be further assessed. Additionally, the article discusses the immune evasion capabilities of the emerging XBB sublineages of the virus and suggests the need for the development of broad-spectrum COVID-19 vaccines. [Extracted from the article]
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- 2024
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15. Genomic Evidence for the Nonpathogenic State in HIV-1–Infected Northern Pig-Tailed Macaques
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Wei Pang, Yong Shao, Xiao-Lin Zhuang, Ying Lu, Wen-Qiang He, Hong-Yi Zheng, Rong Xin, Ming-Xu Zhang, Xiao-Liang Zhang, Jia-Hao Song, Ren-Rong Tian, Fan Shen, Yi-Hui Li, Zu-Jiang Zhao, Dong-Dong Wu, and Yong-Tang Zheng
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Genetics ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics - Abstract
HIV-1 is a highly host-specific retrovirus that infects humans but not most nonhuman primates. Thus, the lack of a suitable primate model that can be directly infected with HIV-1 hinders HIV-1/AIDS research. In the previous study, we have found that the northern pig-tailed macaques (NPMs) are susceptible to HIV-1 infection but show a nonpathogenic state. In this study, to understand this macaque–HIV-1 interaction, we assembled a de novo genome and longitudinal transcriptome for this species during the course of HIV-1 infection. Using comparative genomic analysis, a positively selected gene, Toll-like receptor 8, was identified with a weak ability to induce an inflammatory response in this macaque. In addition, an interferon-stimulated gene, interferon alpha inducible protein 27, was upregulated in acute HIV-1 infection and acquired an enhanced ability to inhibit HIV-1 replication compared with its human ortholog. These findings coincide with the observation of persistently downregulated immune activation and low viral replication and can partially explain the AIDS-free state in this macaque following HIV-1 infection. This study identified a number of unexplored host genes that may hamper HIV-1 replication and pathogenicity in NPMs and provided new insights into the host defense mechanisms in cross-species infection of HIV-1. This work will facilitate the adoption of NPM as a feasible animal model for HIV-1/AIDS research.
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- 2023
16. Significant neutralizing escapes of Omicron and its sublineages in SARS‐CoV‐2‐infected individuals vaccinated with inactivated vaccines
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Fan Shen, Cui‐Xian Yang, Ying Lu, Mi Zhang, Ren‐Rong Tian, Xing‐Qi Dong, An‐Qi Li, Yong‐Tang Zheng, and Wei Pang
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Infectious Diseases ,Virology - Published
- 2023
17. Stability of SARS-CoV-2 on the Surfaces of Three Meats in the Setting That Simulates the Cold Chain Transportation
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Mei Qin Liu, Rong Hua Luo, Bei Li, Xiao li Feng, Ren Rong Tian, Hao Feng Lin, Zhengli Shi, Hong Yi Zheng, Xing-Lou Yang, Ren Di Jiang, Yu Hai Bi, and Yong-Tang Zheng
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2019-20 coronavirus outbreak ,Meat ,Letter ,Coronavirus disease 2019 (COVID-19) ,Refrigeration ,SARS-CoV-2 ,Virology ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Immunology ,Molecular Medicine ,Biology ,Cold chain - Published
- 2021
18. Plasma Virome Reveals Blooms and Transmission of Anellovirus in Intravenous Drug Users with HIV-1, HCV, and/or HBV Infections
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Yanpeng Li, Le Cao, Mei Ye, Rong Xu, Xin Chen, Yingying Ma, Ren-Rong Tian, Feng-Liang Liu, Peng Zhang, Yi-Qun Kuang, Yong-Tang Zheng, and Chiyu Zhang
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Microbiology (medical) ,Hepatitis B virus ,General Immunology and Microbiology ,Ecology ,Physiology ,Virome ,HIV Infections ,Cell Biology ,Hepacivirus ,Hepatitis B ,Anelloviridae ,Hepatitis C ,Drug Users ,Infectious Diseases ,Genetics ,HIV-1 ,Humans ,Substance Abuse, Intravenous ,Phylogeny - Abstract
Intravenous drug users (IDUs) are a high-risk group for HIV-1, hepatitis C virus (HCV), and hepatitis B virus (HBV) infections, which are the leading causes of death in IDUs. However, the plasma virome of IDUs and how it is influenced by above viral infections remain unclear. Using viral metagenomics, we determined the plasma virome of IDUs and its association with HIV-1, HCV, and/or HBV infections. Compared with healthy individuals, IDUs especially those with major viral infections had higher viral abundance and diversity.
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- 2022
19. Exploration of a Sequential Gp140-Gp145 Immunization Regimen with Heterologous Envs to Induce a Protective Cross-Reactive HIV Neutralizing Antibody Response In Non-human Primates
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Jianqing Xu, Qinyun Chen, Jing Wang, Wenjun Wang, Yanmin Wan, Xiaoyan Zhang, Xiangqing Ding, Kangli Cao, Chen Zhao, Ren-rong Tian, Mingzhao Zhu, Yong-Tang Zheng, and Yanqin Ren
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Immunology ,Heterologous ,Viremia ,HIV Infections ,Biology ,HIV Antibodies ,Sequential immunization ,chemistry.chemical_compound ,Mice ,Nanoparticle ,Virology ,medicine ,Animals ,HIV vaccine ,Neutralizing antibody ,Broadly neutralizing antibodies (bnAbs) ,Human immunodeficiency virus type 1 (HIV-1) ,AIDS Vaccines ,env Gene Products, Human Immunodeficiency Virus ,biology.organism_classification ,medicine.disease ,Antibodies, Neutralizing ,Macaca mulatta ,Regimen ,Rhesus macaque ,chemistry ,Immunization ,biology.protein ,HIV-1 ,Molecular Medicine ,Native-like Env trimers ,Vaccinia ,Vaccine ,Research Article - Abstract
Raising a heterologous tier 2 neutralizing antibody (nAb) response remains a daunting task for HIV vaccine development. In this study, we explored the utility of diverse HIV-1 envelope (Env) immunogens in a sequential immunization scheme as a solution to this task. This exploration stemmed from the rationale that gp145, a membrane-bound truncation form of HIV Env, may facilitate the focusing of induced antibody response on neutralizing epitopes when sequentially combined with the soluble gp140 form as immunogens in a prime-boost mode. We first showed that gp140 DNA prime-gp145 Tiantan vaccinia (TV) boost likely represents a general format for inducing potent nAb response in mice. However, when examined in rhesus macaque, this modality showed little effectiveness. To improve the efficacy, we extended the original modality by adding a strong protein boost, namely native-like SOSIP.664 trimer displayed on ferritin-based nanoparticle (NP), which was generated by a newly developed click approach. The resulting three-immunization regimen succeeded in eliciting tier-2 nAb response with substantial breadth when implemented in rhesus macaque over a short 8-week schedule. Importantly, the elicited nAb response was able to effectively contain viremia upon a heterologous SHIV challenge. Collectively, our studies highlighted that diversification of Env immunogens, in both types and formulations, under the framework of a sequential immunization scheme might open new opportunity toward HIV vaccine development. Electronic supplementary material The online version of this article (10.1007/s12250-021-00361-3) contains supplementary material, which is available to authorized users.
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- 2021
20. Lower respiratory tract samples are reliable for severe acute respiratory syndrome coronavirus 2 nucleic acid diagnosis and animal model study
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Jiafa Liu, Ren-Rong Tian, Yong-Tang Zheng, Rong-Hua Luo, Xingqi Dong, Jia-Li Wang, Ling Xu, Hong-li Fan, Dandan Yu, Jianjian Li, Ming-Hua Li, Xiao-Li Feng, Mi Zhang, Hong-Yi Zheng, Zilei Duan, and Cui-Xian Yang
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viruses ,Antibodies, Viral ,Article ,Specimen Handling ,COVID-19 Testing ,Predictive Value of Tests ,Throat ,lcsh:Zoology ,Diagnosis ,medicine ,Animals ,Humans ,Animal model ,lcsh:QL1-991 ,Longitudinal Studies ,skin and connective tissue diseases ,Ecology, Evolution, Behavior and Systematics ,Ecology ,biology ,business.industry ,SARS-CoV-2 ,Sputum ,virus diseases ,COVID-19 ,Haplorhini ,respiratory system ,respiratory tract diseases ,Disease Models, Animal ,medicine.anatomical_structure ,Immunoglobulin M ,Predictive value of tests ,Immunology ,biology.protein ,Nucleic acid ,Pharynx ,Animal Science and Zoology ,Antibody ,medicine.symptom ,business ,Viral load ,Respiratory tract - Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) continue to impact countries worldwide. At present, inadequate diagnosis and unreliable evaluation systems hinder the implementation and development of effective prevention and treatment strategies. Here, we conducted a horizontal and longitudinal study comparing the detection rates of SARS-CoV-2 nucleic acid in different types of samples collected from COVID-19 patients and SARS-CoV-2-infected monkeys. We also detected anti-SARS-CoV-2 antibodies in the above clinical and animal model samples to identify a reliable approach for the accurate diagnosis of SARS-CoV-2 infection. Results showed that, regardless of clinical symptoms, the highest detection levels of viral nucleic acid were found in sputum and tracheal brush samples, resulting in a high and stable diagnosis rate. Anti-SARS-CoV-2 immunoglobulin M (IgM) and G (IgG) antibodies were not detected in 6.90% of COVID-19 patients. Furthermore, integration of nucleic acid detection results from the various sample types did not improve the diagnosis rate. Moreover, dynamic changes in SARS-CoV-2 viral load were more obvious in sputum and tracheal brushes than in nasal and throat swabs. Thus, SARS-CoV-2 nucleic acid detection in sputum and tracheal brushes was the least affected by infection route, disease progression, and individual differences. Therefore, SARS-CoV-2 nucleic acid detection using lower respiratory tract samples alone is reliable for COVID-19 diagnosis and study.新型冠状病毒(SARS-CoV-2)及其造成的肺炎(COVID-19)持续严重影响世界各国。稳定可靠的诊断方法和评价系统的欠缺严重阻碍了有效预防和治疗策略的实施和发展。该研究通过横向和纵向研究,比较分析来源于COVID-19患者和SARS-CoV-2感染猴的不同类型样本中SARS-CoV-2的核酸检出率,分析COVID-19患者和SARS-CoV-2感染猴血清中抗SARS-CoV-2抗体的阳性率,以评估SARS-CoV-2感染诊断方法的可靠性。结果显示无论感染者的临床症状如何,痰液和气管刷样品中病毒核酸检出率较高,感染确诊率高,诊断结果稳定。而6.90% COVID-19患者血清中未检测到抗SARS-CoV-2免疫球蛋白M和G。此外,同时采集不同类型样本并结合其核酸检测的结果并不能提高诊断率。另外,与鼻拭子和咽拭子相比,痰和气管刷中SARS-CoV-2病毒载量持续时间较长,动态变化较明显。因此,痰和气管刷中SARS-CoV-2核酸检测受感染途径、疾病进展和个体差异的影响较小,用下呼吸道标本进行SARS-CoV-2核酸检测是SARS-CoV-2感染诊断和研究的可靠依据。.
- Published
- 2021
21. Northern pig-tailed macaques (Macaca leonina) infected with SARS-CoV-2 show rapid viral clearance and persistent immune response
- Author
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Chao Liu, Xiao-Li Feng, Jian-Bao Han, Feng-Liang Liu, Hong-Yi Zheng, Rong-Hua Luo, Ren-Rong Tian, Lin Jin, Tian-Zhang Song, Xiang Yang, Yong-Tang Zheng, Hou-Rong Cai, and Ming-Hua Li
- Subjects
2019-20 coronavirus outbreak ,Ecology ,biology ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Interleukin-1beta ,Macaca nemestrina ,Alpha interferon ,biology.organism_classification ,Virology ,Macaca leonina ,Immune system ,Animal Science and Zoology ,Ecology, Evolution, Behavior and Systematics - Published
- 2021
22. Novel Triazolopyridine-Based Bromodomain and Extra-Terminal Domain Inhibitors as Potent HIV Latency-Reversing Agents
- Author
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Yan-Kai Wang, Xu-Sheng Huang, Hai-Peng Yu, Meng-Di Ma, Rong-Zhen Wu, Wei Hu, Zhong Li, Zhi-Yu Li, Rong-Hua Luo, Ren-Rong Tian, Tai-Fu Xiao, Liu-Meng Yang, Yong-Tang Zheng, and Xun Li
- Subjects
History ,Polymers and Plastics ,Business and International Management ,Industrial and Manufacturing Engineering - Published
- 2022
23. Delayed severe cytokine storm and immune cell infiltration in SARS-CoV-2-infected aged Chinese rhesus macaques
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Feng-Liang Liu, Lin Jin, Jian-Bao Han, Ming-Hua Li, Hou-Rong Cai, Chao Liu, Xiang Yang, Hong-Yi Zheng, Ren-Rong Tian, Tian-Zhang Song, Xiao-Li Feng, Rong-Hua Luo, and Yong-Tang Zheng
- Subjects
0301 basic medicine ,Aging ,T-Lymphocytes ,Pneumonia, Viral ,Inflammation ,Severe Acute Respiratory Syndrome ,Virus Replication ,03 medical and health sciences ,Betacoronavirus ,0302 clinical medicine ,Immune system ,Elderly ,lcsh:Zoology ,medicine ,Animals ,lcsh:QL1-991 ,Immune response ,Lung ,Pandemics ,Ecology, Evolution, Behavior and Systematics ,Ecology ,business.industry ,SARS-CoV-2 ,Monkey Diseases ,Age Factors ,COVID-19 ,Non-human primate animal model ,Articles ,Viral Load ,medicine.disease ,Macaca mulatta ,030104 developmental biology ,medicine.anatomical_structure ,Viral replication ,Immunology ,Cytokines ,Animal Science and Zoology ,medicine.symptom ,Cytokine storm ,business ,Coronavirus Infections ,Viral load ,Infiltration (medical) ,030217 neurology & neurosurgery ,CD8 - Abstract
As of June 2020, Coronavirus Disease 2019 (COVID-19) has killed an estimated 440 000 people worldwide, 74% of whom were aged ≥65 years, making age the most significant risk factor for death caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To examine the effect of age on death, we established a SARS-CoV-2 infection model in Chinese rhesus macaques ( Macaca mulatta) of varied ages. Results indicated that infected young macaques manifested impaired respiratory function, active viral replication, severe lung damage, and infiltration of CD11b + and CD8 + cells in lungs at one-week post infection (wpi), but also recovered rapidly at 2 wpi. In contrast, aged macaques demonstrated delayed immune responses with a more severe cytokine storm, increased infiltration of CD11b + cells, and persistent infiltration of CD8 + cells in the lungs at 2 wpi. In addition, peripheral blood T cells from aged macaques showed greater inflammation and chemotaxis, but weaker antiviral functions than that in cells from young macaques. Thus, the delayed but more severe cytokine storm and higher immune cell infiltration may explain the poorer prognosis of older aged patients suffering SARS-CoV-2 infection.
- Published
- 2020
24. Glucose Metabolism Disorder Induces Spermatogenic Dysfunction in Northern Pig-Tailed Macaques (Macaca leonina) With Long-Term SIVmac239 Infection
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Ren-Rong Tian, Yong-Tang Zheng, Wei Pang, Ming-Xu Zhang, Tian-Zhang Song, Han-Dan Zhang, and Xue-Hui Wang
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Male ,endocrine system ,medicine.medical_specialty ,glucose metabolism ,Endocrinology, Diabetes and Metabolism ,Simian Acquired Immunodeficiency Syndrome ,Carbohydrate metabolism ,Biology ,medicine.disease_cause ,Diseases of the endocrine glands. Clinical endocrinology ,Cachexia ,Macaca leonina ,Follicle-stimulating hormone ,Endocrinology ,Glucose Metabolism Disorder ,Insulin-Secreting Cells ,Internal medicine ,medicine ,Animals ,Insulin ,Spermatogenesis ,Infertility, Male ,Original Research ,Glucose Metabolism Disorders ,Hormone Imbalance ,geography ,geography.geographical_feature_category ,Simian immunodeficiency virus ,RC648-665 ,northern pig-tailed macaques ,Sertoli cell ,Islet ,medicine.disease ,Semen Analysis ,Glucose ,medicine.anatomical_structure ,SIVmac239 ,spermatogenic dysfunction ,Simian Immunodeficiency Virus ,Macaca nemestrina - Abstract
Although spermatogenic dysfunction is widely found in patients with human immunodeficiency virus (HIV), the underlying reasons remain unclear. Thus far, potential hypotheses involving viral reservoirs, testicular inflammation, hormone imbalance, and cachexia show inconsistent correlation with spermatogenic dysfunction. Here, northern pig-tailed macaques (NPMs) exhibited marked spermatogenic dysfunction after long-term infection with simian immunodeficiency virus (SIVmac239), with significant decreases in Johnsen scores, differentiated spermatogonial stem cells, and testicular proliferating cells. The above hypotheses were also evaluated. Results showed no differences between SIV− and SIV+ NPMs, except for an increase in follicle stimulating hormone (FSH) during SIV infection, which had no direct effect on the testes. However, long-term SIVmac239 infection undermined pancreatic islet β cell function, partly represented by significant reductions in cellular counts and autophagy levels. Pancreatic islet β cell dysfunction led to glucose metabolism disorder at the whole-body level, which inhibited lactate production by Sertoli cells in testicular tissue. As lactate is the main energy substrate for developing germ cells, its decrease was strongly correlated with spermatogenic dysfunction. Therefore, glucose metabolism disorder appears to be a primary cause of spermatogenic dysfunction in NPMs with long-term SIVmac239 infection.
- Published
- 2021
25. Pro-inflammatory microenvironment and systemic accumulation of CXCR3+ cell exacerbate lung pathology of old rhesus macaques infected with SARS-CoV-2
- Author
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Feng-Liang Liu, Yu-Hua Ma, Ming-Hua Li, Xiao-Yan He, Xiao-Li Feng, Tian-Zhang Song, Xiang Yang, Hong-Yi Zheng, Yong-Tang Zheng, Chao Liu, Wei Li, Rong-Hua Luo, Ren-Rong Tian, and Jian-Bao Han
- Subjects
Male ,Cancer Research ,Receptors, CXCR3 ,QH301-705.5 ,T cell ,Alpha interferon ,Inflammation ,CD8-Positive T-Lymphocytes ,CXCR3 ,Article ,Chemokine receptor ,Genetics ,Animals ,Medicine ,Biology (General) ,skin and connective tissue diseases ,Interleukin 6 ,Lung ,biology ,Interleukin-6 ,SARS-CoV-2 ,business.industry ,COVID-19 ,Interferon-alpha ,Macaca mulatta ,Disease Models, Animal ,medicine.anatomical_structure ,Cellular Microenvironment ,Apoptosis ,Immunology ,biology.protein ,Infectious diseases ,Angiotensin-Converting Enzyme 2 ,medicine.symptom ,Infection ,business ,CD8 - Abstract
Understanding the pathological features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in an animal model is crucial for the treatment of coronavirus disease 2019 (COVID-19). Here, we compared immunopathological changes in young and old rhesus macaques (RMs) before and after SARS-CoV-2 infection at the tissue level. Quantitative analysis of multiplex immunofluorescence staining images of formalin-fixed paraffin-embedded (FFPE) sections showed that SARS-CoV-2 infection specifically induced elevated levels of apoptosis, autophagy, and nuclear factor kappa-B (NF-κB) activation of angiotensin-converting enzyme 2 (ACE2)+ cells, and increased interferon α (IFN-α)- and interleukin 6 (IL-6)-secreting cells and C-X-C motif chemokine receptor 3 (CXCR3)+ cells in lung tissue of old RMs. This pathological pattern, which may be related to the age-related pro-inflammatory microenvironment in both lungs and spleens, was significantly correlated with the systemic accumulation of CXCR3+ cells in lungs, spleens, and peripheral blood. Furthermore, the ratio of CXCR3+ to T-box protein expression in T cell (T-bet)+ (CXCR3+/T-bet+ ratio) in CD8+ cells may be used as a predictor of severe COVID-19. These findings uncovered the impact of aging on the immunopathology of early SARS-CoV-2 infection and demonstrated the potential application of CXCR3+ cells in predicting severe COVID-19.
- Published
- 2021
26. Cell membrane skeletal protein 4.1R participates in entry of Zika virus into cells
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Liu-Meng Yang, Qiao-Zhen Kang, Yong-Tang Zheng, Wen-Cong Gao, Liu Xin, Shan Su, Ren-Rong Tian, Kai-Xuan Qiao, and Chang-Bo Zheng
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Host cell membrane ,Cancer Research ,Immunoprecipitation ,Zika Virus Infection ,viruses ,Cell Membrane ,Membrane Proteins ,Zika Virus ,Biology ,Virus Internalization ,biology.organism_classification ,Virus Replication ,Virology ,Virus ,Zika virus ,Cell membrane ,Flavivirus ,Cytoskeletal Proteins ,Infectious Diseases ,medicine.anatomical_structure ,Viral entry ,medicine ,Animals ,Spectrin - Abstract
Zika virus (ZIKV) is a typical mosquito-borne flavivirus known to cause severe fetal microcephaly and adult Guillain-Barre syndrome. Currently, there are no specific drugs or licensed vaccines available for ZIKV infection, and further research is required to identify host cell proteins involved in the virus's life cycle. Viruses are known to use host cell membrane skeletal proteins, such as actin and spectrin, to complete cell entry, transportation, and release. Here, based on immunoprecipitation, the Axl and ZIKV envelope (E) protein were shown to interact with the cell membrane skeleton protein 4.1R. Furthermore, deletion of 4.1R significantly reduced virus titer and viral protein synthesis. Our study showed that 4.1R is an important host cell protein during ZIKV infection and may be involved in the process of viral entry into host cells.
- Published
- 2021
27. Author Correction: Successful implementation of intestinal resection and anastomosis in non-human primates suggests the possibility of longitudinal intestinal research
- Author
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Xue-Hui Wang, Yong-Tang Zheng, Tian-Zhang Song, Lei Li, and Ren-Rong Tian
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0301 basic medicine ,Pathology ,medicine.medical_specialty ,MEDLINE ,H&E stain ,Anastomosis ,Immunofluorescence ,Flow cytometry ,03 medical and health sciences ,Nursing care ,0302 clinical medicine ,Immune system ,Biopsy, Surgery ,Biopsy ,lcsh:Zoology ,Animals ,Homeostasis ,Medicine ,030212 general & internal medicine ,lcsh:QL1-991 ,Letters to the Editor ,Pathological ,Ecology, Evolution, Behavior and Systematics ,Confusion ,Jejunal resection and anastomosis ,Ecology ,medicine.diagnostic_test ,Rhesus macaques ,business.industry ,Published Erratum ,General surgery ,Anastomosis, Surgical ,Monkey Diseases ,Correction ,Macaca mulatta ,Jejunum ,030104 developmental biology ,Immune System ,Animal Science and Zoology ,Surgery ,Intestinal resection ,medicine.symptom ,business - Abstract
Intestinal biopsy is a basic experimental method for studying pathological changes in the intestinal tract during human immunodeficiency virus (HIV) infection. In this study, jejunal resection and anastomosis were successfully performed in 12 Chinese rhesus macaques (Macaca mulatta). The sampled gut tissues were then examined by hematoxylin and eosin (H&E) staining, electron microscopy, flow cytometry, immunofluorescence detection, and RNA quality analysis to ensure suitability for histological, physiological, pathological, and immunological detection, as well as mechanistic analysis at the cellular and molecular level. Importantly, the surgery did not affect the ratio or number of immune cells in peripheral blood or the concentration of lipids, proteins, and vitamins in plasma, which are important indicators of nutritional status. Our results thus indicated that jejunal resection and anastomosis are feasible, and that immune homeostasis and intestinal barrier integrity are not altered by surgery. All macaques recovered well (except for one), with no postoperative complications. Therefore, this animal surgery may be applicable for longitudinal intestinal research related to diseases such as acquired immunodeficiency syndrome (AIDS).
- Published
- 2021
28. Inherited OKT4 epitope deficiency in a Chinese rhesus macaque
- Author
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Zheng-Fei Hu, Ren-Rong Tian, Ming-Liang Zhao, Yun Wang, Ben-Bo Liu, and Yong-Tang Zheng
- Subjects
Genetics ,chemistry.chemical_classification ,education.field_of_study ,General Veterinary ,biology ,Transition (genetics) ,Population ,hemic and immune systems ,chemical and pharmacologic phenomena ,biology.organism_classification ,Phenotype ,Macaca mulatta ,Epitope ,Thymine ,Amino acid ,Rhesus macaque ,chemistry.chemical_compound ,Epitopes ,chemistry ,CD4 Antigens ,Animals ,Animal Science and Zoology ,education ,Cytosine - Abstract
OKT4 is an important epitope of the CD4 molecular. Amino acid mutations in the CD4V3 region result in deficiency of the OKT4 epitope in human. Here, we firstly reported a case of hereditary deficiency of OKT4 epitope in an inbred Chinese rhesus macaque family. This epitope deficiency is due to cytosine to thymine transition and homozygote at the nucleotide position 793 of CD4 coding sequences, which leads to the replace of arginine at 265th position of CD4 molecule by tryptophan. The results reveal that OKT4 epitope deficiency is a very old phenotype and may be parentally inherited, and emphasize the importance of avoiding inbreeding in primate population breeding.
- Published
- 2021
29. Longitudinal transcriptome analyses show robust T cell immunity during recovery from COVID-19
- Author
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Xiao Lu Li, Xi Cheng Wang, Cui Xian Yang, Gui Mei Li, Min Xu, Yu Qi He, Zhao Li Ding, Xing Qi Dong, Jian Jian Li, Yong-Gang Yao, Hong Yi Zheng, Ren Rong Tian, Yong-Tang Zheng, and Mi Zhang
- Subjects
0301 basic medicine ,Male ,Cancer Research ,T-Lymphocytes ,lcsh:Medicine ,RNA-Seq ,Biology ,Genome informatics ,Peripheral blood mononuclear cell ,Article ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Interferon ,microRNA ,Genetics ,medicine ,Humans ,lcsh:QH301-705.5 ,SARS-CoV-2 ,lcsh:R ,RNA ,COVID-19 ,Immunity, Humoral ,Transcription Factor AP-1 ,MicroRNAs ,030104 developmental biology ,lcsh:Biology (General) ,030220 oncology & carcinogenesis ,Humoral immunity ,Immunology ,Leukocytes, Mononuclear ,Infectious diseases ,Female ,RNA, Long Noncoding ,medicine.drug - Abstract
Understanding the processes of immune regulation in patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial for improving treatment. Here, we performed longitudinal whole-transcriptome RNA sequencing on peripheral blood mononuclear cell (PBMC) samples from 18 patients with coronavirus disease 2019 (COVID-19) during their treatment, convalescence, and rehabilitation. After analyzing the regulatory networks of differentially expressed messenger RNAs (mRNAs), microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) between the different clinical stages, we found that humoral immunity and type I interferon response were significantly downregulated, while robust T-cell activation and differentiation at the whole transcriptome level constituted the main events that occurred during recovery from COVID-19. The formation of this T cell immune response might be driven by the activation of activating protein-1 (AP-1) related signaling pathway and was weakly affected by other clinical features. These findings uncovered the dynamic pattern of immune responses and indicated the key role of T cell immunity in the creation of immune protection against this disease.
- Published
- 2020
30. HIV-1 can infect northern pig-tailed macaques (Macaca leonina) and form viral reservoirs in vivo
- Author
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Ming Xu Zhang, Wei Pang, Xiao Ming Liu, Yong-Tang Zheng, Ai Hua Lei, Hong Yi Zheng, Lin Tao Zhang, Jia Hao Song, Ren Rong Tian, Guangxia Gao, Xiao-Liang Zhang, Gao Hong Zhang, Lishan Su, Liguo Zhang, Jia Wu Zhu, and Jin Jiang
- Subjects
0301 basic medicine ,Multidisciplinary ,biology ,Human immunodeficiency virus (HIV) ,virus diseases ,Viremia ,medicine.disease ,biology.organism_classification ,medicine.disease_cause ,Peripheral blood mononuclear cell ,Virology ,03 medical and health sciences ,Macaca leonina ,chemistry.chemical_compound ,030104 developmental biology ,Lymphatic system ,chemistry ,In vivo ,medicine ,Prostratin ,Ex vivo - Abstract
Viral reservoirs of HIV-1 are a major obstacle for curing AIDS. The novel animal models that can be directly infected with HIV-1 will contribute to develop effective strategies for eradicating infections. Here, we inoculated 4 northern pig-tailed macaques (NPM) with the HIV-1 strain HIV-1NL4.3 and monitored the infection for approximately 3 years (150 weeks). The HIV-1-infected NPMs showed transient viremia for about 10 weeks after infection. However, cell-associated proviral DNA and viral RNA persisted in the peripheral blood and lymphoid organs for about 3 years. Moreover, replication-competent HIV-1 could be successfully recovered from peripheral blood mononuclear cells (PBMCs) during long-term infection. The numbers of resting CD4+ T cells in HIV-1 infected NPMs harboring proviruses fell within a range of 2- to 3-log10 per million cells, and these proviruses could be reactivated both ex vivo and in vivo in response to co-stimulation with the latency-reversing agents JQ1 and prostratin. Our results suggested that NPMs can be infected with HIV-1 and a long-term viral reservoir was formed in NPMs, which might serve as a potential model for HIV-1 reservoir research.
- Published
- 2017
31. Annotation and cluster analysis of spatiotemporal- and sex-related lncRNA expression in rhesus macaque brain
- Author
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Longbao Lv, Jian Ma, Zhengbo Wang, Ying Zhang, Dong Chen, Xiangting Wang, Kaiyu Xu, Yi Zhang, Yong-Tang Zheng, Jing Wu, Jiali Li, Siling Liu, Chao Cheng, Liu-Meng Yang, Xintian Hu, Ren-Rong Tian, and Bowen Zhang
- Subjects
Male ,Resource ,0301 basic medicine ,Computational biology ,Macaque ,Epigenesis, Genetic ,03 medical and health sciences ,0302 clinical medicine ,biology.animal ,Genetics ,medicine ,Animals ,Humans ,RNA, Messenger ,Epigenetics ,Genetics (clinical) ,Regulation of gene expression ,Messenger RNA ,biology ,Brain ,Molecular Sequence Annotation ,biology.organism_classification ,Lncrna expression ,Macaca mulatta ,Cap analysis gene expression ,Rhesus macaque ,030104 developmental biology ,medicine.anatomical_structure ,Gene Expression Regulation ,Cerebral cortex ,Multigene Family ,Female ,RNA, Long Noncoding ,sense organs ,030217 neurology & neurosurgery - Abstract
Long noncoding RNAs (lncRNAs) mediate important epigenetic regulation in a wide range of biological processes and diseases. We applied comprehensive analyses of RNA-seq and CAGE-seq (cap analysis of gene expression and sequencing) to characterize the dynamic changes in lncRNA expression in rhesus macaque (Macaca mulatta) brain in four representative age groups. We identified 18 anatomically diverse lncRNA modules and 14 mRNA modules representing spatial, age, and sex specificities. Spatiotemporal- and sex-biased changes in lncRNA expression were generally higher than those observed in mRNA expression. A negative correlation between lncRNA and mRNA expression in cerebral cortex was observed and functionally validated. Our findings offer a fresh insight into spatial-, age-, and sex-biased changes in lncRNA expression in macaque brain and suggest that the changes represent a previously unappreciated regulatory system that potentially contributes to brain development and aging.
- Published
- 2017
32. CD24Fc protects against viral pneumonia in simian immunodeficiency virus-infected Chinese rhesus monkeys
- Author
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Ming-Xu Zhang, Pan Zheng, Xianfeng Fang, Dongling Li, Yang Liu, Liguo Zhang, Yong-Tang Zheng, Ren-Rong Tian, and Mingyue Liu
- Subjects
2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Pneumonia, Viral ,Immunology ,Simian Acquired Immunodeficiency Syndrome ,medicine.disease_cause ,Antigens, CD ,Correspondence ,Animals ,Immunology and Allergy ,Medicine ,Lung ,business.industry ,Simian immunodeficiency virus ,medicine.disease ,ANTIGENS CD ,Macaca mulatta ,Virology ,Infectious Diseases ,medicine.anatomical_structure ,Viral pneumonia ,Simian Immunodeficiency Virus ,business ,Immunosuppression - Published
- 2020
33. Northern pig-tailed macaques (Macaca leonina) infected with SARS-CoV-2 show rapid viral clearance and persistent immune response.
- Author
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Tian-Zhang Song, Hong-Yi Zheng, Jian-Bao Han, Xiao-Li Feng, Feng-Liang Liu, Xiang Yang, Lin Jin, Rong-Hua Luo, Ren-Rong Tian, Chao Liu, Ming-Hua Li, Hou-Rong Cai, and Yong-Tang Zheng
- Subjects
COVID-19 ,PIG-tailed macaque ,INTERFERONS - Published
- 2021
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34. CD24 and Fc fusion protein protects SIVmac239-infected Chinese rhesus macaque against progression to AIDS
- Author
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Martin Devenport, Yang Liu, Ming-Xu Zhang, Pan Zheng, Wei Pang, Xiao-Liang Zhang, Jian-Ping Ma, Xiao-Dong Lian, Lin-Tao Zhang, Yong-Tang Zheng, Mei Ye, Liguo Zhang, Mingyue Liu, Ren-Rong Tian, Peng Zhang, Hong-Yi Zheng, and Gao-Hong Zhang
- Subjects
0301 basic medicine ,T cell ,Recombinant Fusion Proteins ,Simian Acquired Immunodeficiency Syndrome ,Inflammation ,Sialic acid binding ,medicine.disease_cause ,Systemic inflammation ,Peripheral blood mononuclear cell ,03 medical and health sciences ,0302 clinical medicine ,Virology ,medicine ,Animals ,Immunologic Factors ,Pharmacology ,business.industry ,CD24 Antigen ,Simian immunodeficiency virus ,Viral Load ,Macaca mulatta ,Survival Analysis ,Immunoglobulin Fc Fragments ,Intestines ,030104 developmental biology ,medicine.anatomical_structure ,Treatment Outcome ,030220 oncology & carcinogenesis ,Immunology ,HIV-1 ,Simian Immunodeficiency Virus ,medicine.symptom ,business ,Viral load ,CD8 - Abstract
Chronic immune activation and systemic inflammation are underlying causes of acquired immunodeficiency syndrome (AIDS). Products of virus replication and microbial translocation, co-infection or opportunistic pathogens, and danger-associated molecular patterns have been reported to contribute to chronic immune activation and inflammation in human immunodeficiency virus type-1/simian immunodeficiency virus (HIV-1/SIV) infection or other disease. To develop new strategies and therapies for HIV-1/AIDS, we tested if the CD24 and Fc fusion protein (CD24Fc), which interacts with danger-associated molecular patterns and sialic acid binding Ig-like lectin to attenuate inflammation, can protect Chinese rhesus macaques (ChRMs) with SIV infection. We found that CD24Fc treatment decreased weight loss, wasting syndrome, intractable diarrhea, and AIDS morbidity and mortality, while it was well tolerated by SIV-infected animals. Corresponding to the elimination of intractable diarrhea, CD24Fc significantly reduced the expression of IL-6 and indoleamine 2, 3-dioxygenase-1 in peripheral blood mononuclear cell and inflammation in the ileum, colon and rectum based on the reduction of inflammatory cells, pathological scores and expression of inflammatory cytokines. Furthermore, although CD24Fc did not restore CD4+ T cell number or significantly change T cell subsets or CD4+ T cell activation, it maintained low levels of plasma soluble CD14, CD8+ T cell activation, viral load and proviral load in the peripheral blood mononuclear cells and marrow. These results suggested that CD24Fc confers protection to SIV-infected ChRMs against progression to AIDS. It was also implied that CD24Fc may be a potential therapeutic approach for the control of HIV-1/AIDS.
- Published
- 2018
35. High immune activation and abnormal expression of cytokines contribute to death of SHIV89.6-infected Chinese rhesus macaques
- Author
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Gao-Hong Zhang, Wei Pang, Hong-Yi Zheng, Ren-Rong Tian, Lin-Tao Zhang, Lin Zhu, Ming-Xu Zhang, Xiao-Liang Zhang, and Yong-Tang Zheng
- Subjects
CD4-Positive T-Lymphocytes ,Male ,medicine.medical_specialty ,Attenuated vaccine ,T cell ,Simian Acquired Immunodeficiency Syndrome ,Interferon-alpha ,General Medicine ,Disease ,Simian immunodeficiency virus ,Biology ,medicine.disease_cause ,Macaca mulatta ,Virology ,Pathogenesis ,Immune system ,Medical microbiology ,medicine.anatomical_structure ,Immunology ,medicine ,Animals ,Cytokines ,Simian Immunodeficiency Virus ,Viral load - Abstract
Chinese rhesus macaques (CRMs) are ideal experimental animals for studying the pathogenesis of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) and for vaccine research. SHIV89.6 has been reported to be an attenuated virus because, in most cases, SHIV89.6 infection only causes limited alteration of immune cells and tissues, and it has been used commonly for vaccine research. After two serial passages in vivo, SHIV (SHIV-89.6P) induces CD4 lymphopenia and an AIDS-like disease with wasting and opportunistic infections. However, the pathogenic ability of SHIV89.6 is not well understood. In this study, we found that 6 of 14 SHIV89.6-infected CRMs died within 127 weeks after infection. We found especially high immune activation, low IFN-α expression, and distinctive cytokine expression profiles in the infected and dead (ID) group of monkeys, while there was only few change in the CD4(+) T counts and distribution of T cell subsets in the ID group monkeys. Also, there was a similar dynamic of viral load between infected and surviving (IS) and ID group monkeys. Furthermore, we found various correlations among immune activation, IFN-α expression, and frequencies of cytokine-secreting cells. These results suggest that SHIV89.6 infections have pathogenic potential in CRMs and that high immune activation and abnormal expression of cytokines contribute to death of SHIV89.6-infected CRMs. This also implies that high immune activation may be relevant to dysfunction of immune cells. It is proposed that high immune activation and dysfunction of immune cells may be good predictors for disease progression and markers for therapy.
- Published
- 2015
36. Predict disease progression from T‐cell phenotypes in northern pig‐tailed macaques (Macaca leonina) during SIVmac239 infection
- Author
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Jia-Hao Song, Tian-Zhang Song, Wei Pang, Min Chen, Yong-Tang Zheng, Ren-Rong Tian, Yu Xiao, Xiao-Dong Lian, Hong-Yi Zheng, Ming-Xu Zhang, and Jin Jiang
- Subjects
0301 basic medicine ,CD4-Positive T-Lymphocytes ,Male ,T cell ,Immunology ,education ,CD4-CD8 Ratio ,Simian Acquired Immunodeficiency Syndrome ,Acute infection ,CD8-Positive T-Lymphocytes ,Plasma viral load ,03 medical and health sciences ,medicine ,Immunology and Allergy ,Animals ,biology ,Disease progression ,Original Articles ,biology.organism_classification ,Virology ,Phenotype ,Peripheral ,Macaca leonina ,030104 developmental biology ,medicine.anatomical_structure ,Simian Immunodeficiency Virus ,Macaca nemestrina - Abstract
Macaca leonina (northern pig-tailed macaques, NPMs) have variable disease progression during SIVmac239 infection. In the present study, we analysed, for the first time, the correlations between T-cell phenotypes and disease progression in NPMs during SIVmac239 infection. In comparison to normal progressors (NPs), slow progressors (SPs) had lower chronic T-cell activation and exhaustion levels. In addition, SPs showed higher peripheral CD4+ T-cell count and CD4 : CD8 ratio, and lower plasma viral load than NPs. CD4+ T-cell count and CD4 : CD8 ratio decreased more sharply in NPs than in SPs. Furthermore, T cells in NPs were more highly differentiated, at least in acute infection, than in SPs. These results indicated that T-cell phenotypes were correlated with disease progression in SIVmac239-infected NPMs and these correlations may provide valuable guidance for the improvement of therapeutic strategies tested in NPMs.
- Published
- 2017
37. Northern pig-tailed macaques (Macaca leonina) maintain superior CD4
- Author
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Ming-Xu, Zhang, Hong-Yi, Zheng, Jin, Jiang, Jia-Hao, Song, Min, Chen, Yu, Xiao, Xiao-Dong, Lian, Tian-Zhang, Song, Ren-Rong, Tian, Wei, Pang, and Yong-Tang, Zheng
- Subjects
CD4-Positive T-Lymphocytes ,Acquired Immunodeficiency Syndrome ,Disease Models, Animal ,T-Lymphocyte Subsets ,HIV-1 ,Simian Acquired Immunodeficiency Syndrome ,Animals ,Homeostasis ,Macaca ,Simian Immunodeficiency Virus ,Viral Load ,Immunologic Memory - Abstract
Gradual depletion of CD4
- Published
- 2017
38. Accelerated disease progression and robust innate host response in aged SIVmac239-infected Chinese rhesus macaques is associated with enhanced immunosenescence
- Author
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Xiao-Dong Lian, Jin Jiang, Xiao-Liang Zhang, Min Chen, Ren-Rong Tian, Wei Pang, Yong-Tang Zheng, Hong-Yi Zheng, Jia-Hao Song, Ming-Xu Zhang, Gao-Hong Zhang, and Lin-Tao Zhang
- Subjects
CD4-Positive T-Lymphocytes ,Male ,0301 basic medicine ,Aging ,Naive T cell ,Immunosenescence ,Science ,Simian Acquired Immunodeficiency Syndrome ,medicine.disease_cause ,Article ,Pathogenesis ,03 medical and health sciences ,Acquired immunodeficiency syndrome (AIDS) ,Immunity ,medicine ,Animals ,Multidisciplinary ,business.industry ,Disease progression ,Viral Load ,Simian immunodeficiency virus ,medicine.disease ,Macaca mulatta ,Virology ,Immunity, Innate ,030104 developmental biology ,Immunology ,Disease Progression ,Medicine ,Simian Immunodeficiency Virus ,business ,Viral load - Abstract
The elderly population infected with HIV-1 is often characterized by the rapid AIDS progression and poor treatment outcome, possibly because of immunosenescence resulting from both HIV infection and aging. However, this hypothesis remains to be fully tested. Here, we studied 6 young and 12 old Chinese rhesus macaques (ChRM) over the course of three months after simian immunodeficiency virus (SIV) SIVmac239 infection. Old ChRM showed a higher risk of accelerated AIDS development than did young macaques, owing to rapidly elevated plasma viral loads and decreased levels of CD4+ T cells. The low frequency of naïve CD4+ T cells before infection was strongly predictive of an increased disease progression, whereas the severe depletion of CD4+ T cells and the rapid proliferation of naïve lymphocytes accelerated the exhaustion of naïve lymphocytes in old ChRM. Moreover, in old ChRM, a robust innate host response with defective regulation was associated with a compensation for naïve T cell depletion and a high level of immune activation. Therefore, we suggest that immunosenescence plays an important role in the accelerated AIDS progression in elderly individuals and that SIV-infected old ChRM may be a favorable model for studying AIDS pathogenesis and researching therapies for elderly AIDS patients.
- Published
- 2017
- Full Text
- View/download PDF
39. Northern pig-tailed macaques (Macaca leonina ) maintain superior CD4+ T-cell homeostasis during SIVmac239 infection
- Author
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Xiao-Dong Lian, Min Chen, Yu Xiao, Hong-Yi Zheng, Jia-Hao Song, Tian-Zhang Song, Ren-Rong Tian, Yong-Tang Zheng, Ming-Xu Zhang, Jin Jiang, and Wei Pang
- Subjects
0301 basic medicine ,Cd4 t cell ,viruses ,animal diseases ,Immunology ,virus diseases ,Biology ,010502 geochemistry & geophysics ,biology.organism_classification ,01 natural sciences ,Virology ,03 medical and health sciences ,Macaca leonina ,030104 developmental biology ,stomatognathic system ,Immunology and Allergy ,Homeostasis ,0105 earth and related environmental sciences - Abstract
Gradual depletion of CD4+ T cells is a typical characteristic of pathogenic SIV infection. Intriguingly, we find a spontaneous CD4+ T-cell homeostasis in northern pig-tailed macaques (Macaca leonina) during SIVmac239 infection.
- Published
- 2018
40. Delayed severe cytokine storm and immune cell infiltration in SARS-CoV-2-infected aged Chinese rhesus macaques.
- Author
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Tian-Zhang Song, Hong-Yi Zheng, Jian-Bao Han, Lin Jin, Xiang Yang, Feng-Liang Liu, Rong-Hua Luo, Ren-Rong Tian, Hou-Rong Cai, Xiao-Li Feng, Chao Liu, Ming-Hua Li, and Yong-Tang Zheng
- Subjects
CYTOKINES ,COVID-19 pandemic ,SARS disease ,IMMUNE response ,CHEMOTAXIS - Abstract
As of June 2020, Coronavirus Disease 2019 (COVID-19) has killed an estimated 440 000 people worldwide, 74% of whom were aged ≥65 years, making age the most significant risk factor for death caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To examine the effect of age on death, we established a SARSCoV- 2 infection model in Chinese rhesus macaques (Macaca mulatta) of varied ages. Results indicated that infected young macaques manifested impaired respiratory function, active viral replication, severe lung damage, and infiltration of CD11b+ and CD8+ cells in lungs at one-week post infection (wpi), but also recovered rapidly at 2 wpi. In contrast, aged macaques demonstrated delayed immune responses with a more severe cytokine storm, increased infiltration of CD11b+ cells, and persistent infiltration of CD8+ cells in the lungs at 2 wpi. In addition, peripheral blood T cells from aged macaques showed greater inflammation and chemotaxis, but weaker antiviral functions than that in cells from young macaques. Thus, the delayed but more severe cytokine storm and higher immune cell infiltration may explain the poorer prognosis of older aged patients suffering SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
41. Successful implementation of intestinal resection and anastomosis in non-human primates suggests the possibility of longitudinal intestinal research.
- Author
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Xue-Hui Wang, Tian-Zhang Song, Lei Li, Ren-Rong Tian, and Yong-Tang Zheng
- Subjects
SURGICAL anastomosis ,SURGICAL excision ,INTESTINES ,RHESUS monkeys ,ELECTRON microscopy - Abstract
The article reports the research study on jejunal resection and anastomosis performed in Chinese rhesus macaques. Topics include that sampled gut tissues were examined by hematoxylin and eosin (H&E) staining, electron microscopy, flow cytometry, immunofluorescence detection, and RNA quality analysis.
- Published
- 2020
- Full Text
- View/download PDF
42. Assignment of the Absolute Configuration ofConcentricolide- Absolute Configuration Determination of Its Bioactive Analogs Using DFT Methods
- Author
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Liang-Bo Li, Ju-Xing Jiang, Ren-Rong Tian, Jie Ren, Hua-Jie Zhu, Charles U. Pittman, Xulin Chen, Tou-Geng Liao, and Si-Ping Jiang
- Subjects
Circular dichroism ,Crystallography ,Concentricolide ,Chemistry ,Stereochemistry ,Organic Chemistry ,Human immunodeficiency virus (HIV) ,medicine ,Absolute configuration ,Physical and Theoretical Chemistry ,Optical rotation ,medicine.disease_cause ,Chirality (chemistry) - Abstract
The configuration of concentricolide was assigned as (S). The configuration of its three analogs, which have anti-HIV-1 activity, were predicted by optical rotation values obtained by the B3LYP/aug-cc-pVDZ//B3LYP/6-31+G(d) and B3LYP/aug-cc-pVDZ//MP2/6-311+G(d) methods. The two methods predict very close optical rotation magnitudes for all three chiral analogs of concentricolide. The two methods were applied in optical rotation predictions for seven other concentricolide analogs. Circular dichroism calculations were performed for four of the seven analogs at the B3LYP/aug-cc-pVDZ level. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
- Published
- 2009
43. Calycosin 7-O-β-D-glucopyranoside, an anti-HIV agent from the roots of Astragalus membranaceus var. mongholicus
- Author
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Mingsong Fan, Chenggang Huang, Chun-Hui Ma, Rui-Rui Wang, Guan Ye, Yong-Tang Zheng, and Ren-Rong Tian
- Subjects
chemistry.chemical_compound ,Calycosin ,chemistry ,Traditional medicine ,Anti-HIV Agent ,Plant Science ,General Chemistry ,Astragalus membranaceus var. mongholicus ,General Biochemistry, Genetics and Molecular Biology - Published
- 2009
44. Prevention and treatment of KSHV-associated diseases with antiviral drugs
- Author
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Qing-jiao Liao, Ren-rong Tian, and Xulin Chen
- Subjects
medicine.medical_specialty ,business.industry ,viruses ,Immunology ,virus diseases ,Treatment options ,medicine.disease ,law.invention ,Medical microbiology ,Randomized controlled trial ,law ,Virology ,Molecular Medicine ,Medicine ,Primary effusion lymphoma ,Sarcoma ,Multicentric Castleman Disease ,business - Abstract
Kaposi’s sarcoma-associated herpesvirus (KSHV) was first identified as the etiologic agent of Kaposi’s sarcoma (KS) in 1994. KSHV infection is necessary, but not sufficient for the development of Kaposi sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman disease (MCD). Advances in the prevention and treatment of KSHV-associated Diseases have been achieved, even though current treatment options are ineffective, or toxic to many affected persons. The identification of new targets for potential future therapies and the randomized trial to evaluate the efficacy of new antivirals are required.
- Published
- 2008
45. Anti-HIV-1 Activities of Hemslecins A and B
- Author
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Gao-Hong Zhang, Jian-Chao Chen, Nai-Fa Liu, Ming-Hua Qiu, Yong-Tang Zheng, De-Sen Li, Yun-Hua Wang, Xu Shen, and Ren-Rong Tian
- Subjects
Anti hiv 1 ,General Medicine ,Biology ,Virology - Published
- 2008
46. Two New C20-Diterpenoid Alkaloids from the Tibetan Medicinal PlantAconitum naviculareStapf
- Author
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Jie Ren, Ren-Rong Tian, Jin-Xin Cao, Shu-Lin Peng, Xulin Chen, Si-Ping Jiang, Jie Zhang, Liang-Bo Li, and Hua-Jie Zhu
- Subjects
Inorganic Chemistry ,Chemistry ,Stereochemistry ,Organic Chemistry ,Drug Discovery ,Physical and Theoretical Chemistry ,Biochemistry ,Two-dimensional nuclear magnetic resonance spectroscopy ,Catalysis ,Terpenoid ,Aconitum naviculare - Abstract
Two new C-20-diterpenoid alkaloids named naviculine A (1) and naviculine B (2), were isolated from Aconitum naviculare STAPF. Their structures were established by spectral methods, especially 2D-NMR spectra (H-1,H-1-COSY, HMQC. HMBC, and NOESY) and DFT methods (at the B3LYP/6-311+ + G(2d,p)//B3LYP/6-31G(d) level). respectively. They were assayed for their anti-HIV-1 activity
- Published
- 2008
47. Anti-HIV-1 Activities of Hemslecins A and B
- Author
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Ren-Rong Tian, Yun-Hua Wang, Jian-Chao Chen, Yong-Tang Zheng, Nai-Fa Liu, De-Sen Li, Gao-Hong Zhang, Xu Shen, and Ming-Hua Qiu
- Subjects
Anti hiv 1 ,Complementary and alternative medicine ,Drug Discovery ,General Medicine ,Virology - Abstract
目的:研究从药用植物金佛山雪胆分离的雪胆素A和雪胆素B两个三萜类化合物的体外抗HIV活性.方法:应用合胞体抑制实验、p24抗原产生的抑制实验、慢性感染细胞和正常细胞间的细胞融合抑制实验等技术检测化合物的体外抗HIV-l活性;利用HIV-l逆转录酶、蛋白酶抑制实验,NCp7锌离子逐出实验探讨化合物的作用机制.结果:雪胆素A和雪胆素B在体外有较好的抑制HIV-l活性,其活性主要表现为:(1)抑制HIV-l诱导合胞体形成,EC50值分别为3.09 μg·mL-1和2.53μg·mL-1;(2)抑制HIV- 急性感染的C8106细胞p24抗原产生,EC50值分别为3.97μg·mL-1和18.90μg·mL-1;(3)抑制HIV-1 慢性感染H9与正常C8166细胞间融合,EC50分别为1.76μg·mL-1和11.95μg·mL-1.雪胆素A和雪胆素B对HIV-l逆转录酶、蛋白酶、NCp7锌离子逐出均没有抑制作用.雪胆素A对HIV-1整合酶有微弱的结合活性,而雪胆素B对HIV-1整合酶没有结合活性.在共培养实验中,雪胆素A和雪胆素B预处理C8166细胞组比未经预处理细胞组能够更有效的抑制HIV-l活性.结论:化合物雪胆素A和雪胆素B体外有较好的抗HIV-1活性,可能主要作用于HIV-1病毒进入细胞阶段.
- Published
- 2008
48. Current status of targets and assays for anti-HIV drug screening
- Author
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Ren-rong Tian, Xulin Chen, and Qing-jiao Liao
- Subjects
Drug ,medicine.medical_specialty ,business.industry ,Public health ,media_common.quotation_subject ,Immunology ,Human immunodeficiency virus (HIV) ,Drug resistance ,Disease ,Pharmacology ,medicine.disease_cause ,medicine.disease ,Medical microbiology ,Acquired immunodeficiency syndrome (AIDS) ,Virology ,medicine ,Anti-hiv drugs ,Molecular Medicine ,business ,Intensive care medicine ,media_common - Abstract
HIV/AIDS is one of the most serious public health challenges globally. Despite the great efforts that are being devoted to prevent, treat and to better understand the disease, it is one of the main causes of morbidity and mortality worldwide. Currently, there are 30 drugs or combinations of drugs approved by FDA. Because of the side-effects, price and drug resistance, it is essential to discover new targets, to develop new technology and to find new anti-HIV drugs. This review summarizes the major targets and assays currently used in anti-HIV drug screening.
- Published
- 2007
49. Translocation of microbes and changes of immunocytes in the gut of rapid- and slow-progressor Chinese rhesus macaques infected with SIVmac239
- Author
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Ren-Rong Tian, Lin-Tao Zhang, Xue-Shan Xia, Guoqing Pan, Yong-Tang Zheng, Xiaoyu Tuo, Wei Pang, Hong-Yi Zheng, and Hou-Jun Xia
- Subjects
0301 basic medicine ,CD4-Positive T-Lymphocytes ,Male ,Phagocytosis ,Immunology ,Simian Acquired Immunodeficiency Syndrome ,Chromosomal translocation ,Biology ,CD8-Positive T-Lymphocytes ,medicine.disease_cause ,Microbiology ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Intestinal mucosa ,medicine ,Extracellular ,Immunology and Allergy ,Animals ,Lymphocyte Count ,Intestinal Mucosa ,Lamina propria ,Macrophages ,Original Articles ,Simian immunodeficiency virus ,Viral Load ,Macaca mulatta ,Gastrointestinal Microbiome ,030104 developmental biology ,medicine.anatomical_structure ,Disease Progression ,Simian Immunodeficiency Virus ,CD8 ,030215 immunology - Abstract
Human/simian immunodeficiency virus (HIV/SIV) infection can cause severe depletion of CD4(+) T cells in both plasma and mucosa; it also results in damage to the gut mucosa barrier, which makes the condition more conducive to microbial translocation. In this study, we used SIV-infected Chinese rhesus macaques to quantify the extent of microbial translocation and the function of immune cells in the entire gastrointestinal tract and to compare their differences between rapid and slow progressors. The results showed that in the slow progressors, microbial products translocated considerably and deeply into the lamina propria of the gut; the tissue macrophages had no significant differences compared with the rapid progressors, but there was a slightly higher percentage of mucosal CD8(+) T cells and a large amount of extracellular microbial products in the lamina propria of the intestinal mucosa of the slow progressors. The data suggested that although microbial translocation increased markedly, the mucosal macrophages and CD8(+) T cells were insufficient to clear the infiltrated microbes in the slow progressors. Also, therapies aimed at suppressing the translocation of microbial products in the mucosa could help to delay the progression of SIV disease.
- Published
- 2015
50. Lipopolysaccharide Increases Immune Activation and Alters T Cell Homeostasis in SHIVB’WHU Chronically Infected Chinese Rhesus Macaque
- Author
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Guang-Ming Liu, Ming-Xu Zhang, Xiao-Liang Zhang, Run-Dong Wu, Ren-Rong Tian, Hong-Yi Zheng, Yong-Tang Zheng, Gao-Hong Zhang, and Wei Pang
- Subjects
CD4-Positive T-Lymphocytes ,Lipopolysaccharides ,Male ,Interleukin 2 ,lcsh:Immunologic diseases. Allergy ,Article Subject ,Lipopolysaccharide ,Programmed Cell Death 1 Receptor ,Immunology ,Simian Acquired Immunodeficiency Syndrome ,CD8-Positive T-Lymphocytes ,Biology ,Lymphocyte Activation ,Virus Replication ,medicine.disease_cause ,Interferon-gamma ,chemistry.chemical_compound ,Immune system ,medicine ,Animals ,Homeostasis ,Humans ,Immunology and Allergy ,Interferon gamma ,Interleukin 4 ,Tumor Necrosis Factor-alpha ,General Medicine ,Simian immunodeficiency virus ,Macaca mulatta ,Immunity, Innate ,Gene Expression Regulation ,chemistry ,Chronic Disease ,Host-Pathogen Interactions ,Interleukin-2 ,Simian Immunodeficiency Virus ,Tumor necrosis factor alpha ,Interleukin-4 ,lcsh:RC581-607 ,Immunologic Memory ,CD8 ,Research Article ,Signal Transduction ,medicine.drug - Abstract
Immune activation plays a significant role in the disease progression of HIV. Microbial products, especially bacterial lipopolysaccharide (LPS), contribute to immune activation. Increasing evidence indicates that T lymphocyte homeostasis disruptions are associated with immune activation. However, the mechanism by which LPS affects disruption of immune response is still not fully understood. Chronically SHIVB’WHU-infected Chinese rhesus macaques received 50 μg/kg body weight LPS in this study. LPS administration affected the virus/host equilibrium by elevating the levels of viral replication and activating T lymphocytes. LPS induced upregulation of CD8+naïve T cells and downregulated the number of CD4+and CD8+T effector memory cells. The downregulated effector memory cells are associated with a lower frequency of monofunctional and polyfunctional cells, and an upregulated programmed cell death-1 (PD-1) expression on CD4+and CD8+T cells was observed in monkeys after LPS stimulation. Our data provide new insights into the function of LPS in the immune activation in SHIV/HIV infection.
- Published
- 2015
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