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Aging induces severe SIV infection accompanied by an increase in follicular CD8+T cells with overactive STAT3 signaling

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Cellular & Molecular Immunology 2022年第9期19卷 1042-1053页

作者： Hong-Yi Zheng Xue-Hui Wang Xiao-Yan He Min Chen Ming-Xu Zhang Xiao-Dong Lian Jia-Hao Song Yan Hu Wei Pang Yun Wang Zheng-Fei Hu Long-Bao Lv Yong-Tang Zheng Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesCenter for Biosafety Mega-ScienceKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan650223China School of Life Sciences University of Science and Technology of ChinaHefeiAnhui230026China Kunming College of Life Science University of Chinese Academy of SciencesKunmingYunnan650204China National Resource Center for Non-Human Primates National Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility)Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan650107China

The number of elderly people living with HIV is increasing globally,and the condition of this population is relatively complicated due to the dual effects of aging and HIV ***,the impact of HIV infection combined with aging on the immune homeostasis of secondary lymphoid organs remains ***,we used the simian immunodeficiency virus mac239(SIVmac239)strain to infect six young and six old Chinese rhesus macaques(ChRMs)and compared the infection characteristics of the two groups in the chronic stage through multiplex immunofluorescence staining of lymph *** results showed that the SIV production and CD4/CD8 ratio inversion in old ChRMs were more severe than those in young ChRMs in both the peripheral blood and the lymph nodes,especially when a large number of CD8+T cells infiltrated the follicles and germinal ***3 in these follicular CXCR5+CD8+T cells was highly activated,with high expression of granzyme B,which might be caused by the severe inflammatory milieu in the follicles of old *** study indicates that aging may be a cofactor involved in SIV-induced immune disorders in secondary lymphoid tissues,affecting the effective antiviral activity of highly enriched follicular CXCR5+CD8+cells.

关键词： SIV Aging Follicle CD8 T cells

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Successful implementation of intestinal resection and anastomosis in non-human primates suggests the possibility of longitudinal intestinal research

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Zoological Research 2020年第4期41卷 449-454页

作者： Xue-Hui Wang Tian-Zhang Song Lei Li Ren-Rong Tian Yong-Tang Zheng School of Life Sciences University of Science and Technology of ChinaHefeiAnhui 230026China Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesCenter for Biosafety Mega-ScienceKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China Dong fang Animal Hospital KunmingYunnan 650228China

DEAR EDITOR,Intestinal biopsy is a basic experimental method for studying pathological changes in the intestinal tract during human immunodeficiency virus(HIV)*** this study,jejunal resection and anastomosis were succ... 详细信息

关键词： anastomosis resection biopsy

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CD24Fc protects against viral pneumonia in simian immunodeficiency virus-infected Chinese rhesus monkeys

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Cellular & Molecular Immunology 2020年第8期17卷 887-888页

作者： Ren-Rong Tian Ming-Xu Zhang Mingyue Liu Xianfeng Fang Dongling Li Liguo Zhang Pan Zheng Yong-Tang Zheng Yang Liu Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences Center for Biosafety Mega-ScienceKunming Institute of ZoologyChinese Academy of SciencesKunming650223YunnanChina Division of Immunotherapy Institute of Human Virology and Department of SurgeryUniversity of Maryland BaltimoreBaltimoreMDUSA OncoImmune Guangzhou Ltd GuangzhouGuangdongChina OncoImmune Suzhou Ltd SuzhouJiangsuChina CAS Key Laboratory for Infection and Immunity Institute of BiophysicsChinese Academy of Sciences100101BeijingChina OncoImmune IncRockvilleMDUSA

Viral pneumonia is a major cause of mortality caused by both systemic and respiratory *** danger-associated molecular patterns(DAMPs)released during cell death in viral infection may cause a self-propagating inflammatory response with lasting lung *** CD24–Siglec 10/G interaction is an emerging immune checkpoint that regulates inflammation caused by DAMPs.1,2,3 While we have demonstrated that fortifying this immune checkpoint can reduce inflammation in the colon,4 joints5 and central nervous system,6 it is unclear whether CD24Fc can protect against *** address this issue,we evaluated the lung pathology of simian immunodeficiency virus(SIV)-infected rhesus monkeys that received either normal saline(NS)or CD24Fc.

关键词： CD24 pneumonia immunodeficiency

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HIV感染与细胞焦亡

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免疫学杂志 2018年第1期34卷 80-85页

作者：陈敏郑永唐中国科学院昆明动物研究所中国科学院动物模型与人类疾病机理重点实验室 650223 中国科学院大学昆明生命科学学院 650204

目前艾滋病(AIDS)被认为是一种慢性疾病。炎症和免疫活化在疾病进展中起了重要作用。细胞焦亡是HIV感染过程中造成CD4^+T细胞死亡的主要程序性细胞死亡方式,并伴随着IL-1β等促炎因子和细胞内容物的释放,引起机体炎症反应。细胞焦亡联... 详细信息

目前艾滋病(AIDS)被认为是一种慢性疾病。炎症和免疫活化在疾病进展中起了重要作用。细胞焦亡是HIV感染过程中造成CD4^+T细胞死亡的主要程序性细胞死亡方式,并伴随着IL-1β等促炎因子和细胞内容物的释放,引起机体炎症反应。细胞焦亡联系起了HIV感染过程中的CD4^+T细胞死亡和炎症反应发生这2个最主要的病理事件。因此,抑制细胞焦亡可能对艾滋患者的治疗有重要意义。本文综述了HIV感染过程中细胞焦亡的发生及其引起的病理性事件,为探索艾滋病患者治疗新策略提供线索。

关键词： HIV AIDS 细胞焦亡细胞凋亡 Caspase活化

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免疫衰老在艾滋病发病中的作用及治疗策略研究进展

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中国免疫学杂志 2017年第10期33卷 1575-1580页

作者：郑宏毅郑永唐中国科学院昆明动物研究所昆明650223

由于HIV感染引起的病理特征同免疫系统的衰老之间具有众多相似性,近年来免疫衰老（Immunosenescence）成为了HIV研究领域的前沿。一方面免疫系统的衰老会减弱免疫反应和免疫监视能力,造成机体对感染性疾病更加敏感和丧失疫苗响应能力[1... 详细信息

由于HIV感染引起的病理特征同免疫系统的衰老之间具有众多相似性,近年来免疫衰老（Immunosenescence）成为了HIV研究领域的前沿。一方面免疫系统的衰老会减弱免疫反应和免疫监视能力,造成机体对感染性疾病更加敏感和丧失疫苗响应能力[1,2]。另一方面HIV持续复制及其引发的慢性免疫活化（Immune activation）与炎症（Inflammation）又会进一步加速免疫衰老,即使长期的抗逆转录病毒治疗也难以遏制这一过程,最终增加感染者罹患老年病和发展为艾滋病的风险[3]。

关键词：抗逆转录病毒治疗免疫衰老艾滋病 HIV感染发病免疫系统响应能力感染性疾病

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Superior intestinal integrity and limited microbial translocation are associated with lower immune activation in SIVmac239-infected northern pig-tailed macaques(Macaca leonina)

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Zoological Research 2019年第6期40卷 522-531页

作者： Ming-Xu Zhang Tian-Zhang Song Hong-Yi Zheng Xue-Hui Wang Ying Lu Han-Dan Zhang Ting Li Wei Pang Yong-Tang Zheng Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province National Kunming High Level Biosafety Research Center for Non-human PrimatesKIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesKunming Institute of ZoologyChinese Academy of SciencesKunming Yunnan 650223China Kunming College of Life Science University of Chinese Academy of SciencesKunming Yunnan 650204China School of Life Sciences University of Science and Technology of ChinaHefei Anhui 230026China KIZ-SU Joint Laboratory of Animal Models and Drug Development College of Pharmaceutical SciencesSoochow UniversitySuzhou Jiangsu 215123China

Microbial translocation is a cause of systemic immune activation in HIV/SIV infection. In the present study, we found a lower CD8+ T cell activation level in Macaca leonina (northern pig-tailed macaques, NPMs) than in Macaca mulatta (Chinese rhesus macaques, ChRMs) during SIVmac239 infection. Furthermore, the levels of plasma LPS-binding protein and soluble CD14 in NPMs were lower than those in ChRMs. Compared with ChRMs, SIV-infected NPMs had lower Chiu scores, representing relatively normal intestinal mucosa. In addition, no obvious damage to the ileum or colon epithelial barrier was observed in either infected or uninfected NPMs, which differed to that found in ChRMs. Furthermore, no significant microbial translocation (Escherichia coli) was detected in the colon or ileum of infected or uninfected NPMs, which again differed to that observed in ChRMs. In conclusion, NPMs retained superior intestinal integrity and limited microbial translocation during SIV infection, which may contribute to their lower immune activation compared with ChRMs.

关键词： Immune activation Intestinal integrity Microbial translocation SIVmac239 Macaca leonina Northern pig-tailed macaques Macaca mulatta Chinese rhesus macaques

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Parasites may exit immunocompromised northern pig-tailed macaques (Macaca leonina)infected with SIVmac239

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Zoological Research 2018年第1期39卷 42-51页

作者： tian-zhang song ming-xu zhang yu-jie xia yu xiao wei pang yong-tang zheng Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming Yunnan 650223China University of Chinese Academy of Sciences Bejing 100049China Kunming Primate Research Center Kunming Institute of ZoologyChinese Academy of SciencesKunming Yunnan 650223China

Parasites can increase infection rates and pathogenicity in immunocompromised human immunodeficiency virus （HIV） patients. However, in vitro studies and epidemiological investigations also suggest that parasites might escape immunocompromised hosts during HIV infection Due to the lack of direct evidence from animal experiments, the effects of immunocompromised hosts parasitic infections on remain unclear. Here we detected 14 different parasites in six northern pig-tailed macaques （NPMs） before or at the 50th week of simian immunodeficiency virus （SIV） infection by ELISA. The NPMs all carried parasites before viral injection. At the 50th week after viral injection, the individuals with negative results in parasitic detection （i.e., 08247 and 08287） were characterized as the Parasites Exit （PE） group, with the other individuals （i.e., 09203, 09211, 10205, and 10225） characterized as the Parasites Remain （PR） group. Compared with the PR group, the NPMs in the PE group showed higher viral loads, lower CD4＋ T cells counts, and lower CD4/CD8 rates. Additionally, the PE group had higher immune activation and immune exhaustion of both CD4~ and CD8~ T cells. Pathological observation showed greater injury to the liver, cecum, colon, spleen, and mesenteric lymph nodes in the PE group This study showed more seriously compromised immunity in the PE group, strongly indicating that parasites might exit an immunocompromised host.

关键词： AIDS Immunocompromised Northernpig-tailed macaque Parasite SIVmac239

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Association of TRIMCyp and TRIM5α from assam macaques leads to a functional trade-off between HIV-1 and N-MLV inhibition

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Science China(Life Sciences) 2018年第8期61卷 954-965页

作者： Dan Mu Jia-Wu Zhu Feng-Liang Liu Hong-Yi Zheng Yong-Tang Zheng Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province Kunming Institute of Zoology Chinese Academy of Sciences Kunming 650223 China Kunming College of Life Science University of Chinese Academy of Sciences Kunming 650204 China Kunming Primate Research Center Chinese Academy of Sciences Kunming 650223 China

TRIM5α restricts retroviruses in a species-specific manner. Cyclophilin A was independently retrotransposed into the TRIM5 loci in different species, leading to the generation of antiviral TRIM5-cyclophilin A(TRIMCyp) proteins. Previously, we found that assam macaques express a TRIMCyp chimera(am TRIMCyp), along with a TRIM5α allelic protein(am TRIM5α). Herein,we investigated the antiviral activity of am TRIMCyp and am TRIM5α individually, as well as their interaction and joint *** TRIMCyp showed a divergent restriction pattern from am TRIM5α. Although both proteins potently restricted the replication of HIV-1, only am TRIM5α inhibited N-MLV. Remarkably, cellular anti-HIV-1 activity increased when am TRIMCyp and am TRIM5α were coexpressed, indicating a synergistic block of HIV-1 replication. Consistently, PMBCs from heterozygous am TRIM5α/TRIMCyp showed stronger resistance to HIV-1 infection than those from am TRIM5α/TRIM5α homozygotes. The anti-HIV-1 synergistic effect was dependent on the am TRIMCyp-am TRIM5α interaction. In contrast, am TRIMCyp completely abrogated the anti-N-MLVactivity mediated by am TRIM5α, showing a dominant-negative effect, indicating that the generation of am TRIMCyp was involved in the trade-off between divergent restriction activities. Our results provide a new paradigm to study functional trade-offs mediated by allelic proteins, a theoretical basis for utilizing animal models with various TRIM5 alleles, as well as novel HIV-1 gene therapy strategies.

关键词： HIV-1 交易猕猴协会相互作用蛋白质学习功能动物模型

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非人灵长类动物:免疫学基础研究到临床应用的桥梁

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中国免疫学杂志 2018年第8期34卷 1121-1130页

作者：郑宏毅郑永唐中国科学院昆明动物研究所昆明650223

非人灵长类动物的免疫学特征与人高度相似,能够解决啮齿类动物模型面临的医学转化困境,在免疫学研究中具有独特优势。常用的非人灵长类动物(如猕猴、平顶猴、食蟹猴、普通狨猴等)在感染免疫、免疫应答、免疫衰老、自身免疫性疾病等研究... 详细信息

非人灵长类动物的免疫学特征与人高度相似,能够解决啮齿类动物模型面临的医学转化困境,在免疫学研究中具有独特优势。常用的非人灵长类动物(如猕猴、平顶猴、食蟹猴、普通狨猴等)在感染免疫、免疫应答、免疫衰老、自身免疫性疾病等研究领域发挥着举足轻重的作用,是连接基础研究与临床应用之间的桥梁。现今非人灵长类动物应用于免疫学研究依然存在诸多问题,但在国内外学者不断的开发过程中被解决,其应用将更加标准化、规模化,更有利于免疫学发展。作为国家战略需求,我们应当抓住这个机会,加大力度支持非人灵长类的免疫学研究,实现中国免疫学的重大突破。

关键词：非人灵长类动物动物模型免疫学传染病免疫应答

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葡萄糖代谢异常导致SIVmac239感染北平顶猴急性期体重变化

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中国实验动物学报 2018年第6期26卷 693-699页

作者：张瀚丹宋天章杨柳萌郑永唐大理大学药学与化学学院云南大理671000 中国科学院昆明动物研究所、云南省活性多肽研究与利用重点实验室/中国科学院动物模型与人类疾病重点实验室国家昆明高等级生物安全灵长类动物实验中心昆明650223

目的探讨艾滋病急性期炎症因子、脂类代谢及葡萄糖代谢对体重的影响。方法检测SIVmac239感染北平顶猴急性期炎症因子(TNF-α、IL-6)、脂类代谢(胆固醇、三酰甘油、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇)及葡萄糖代谢参数(胰岛素、胰... 详细信息

目的探讨艾滋病急性期炎症因子、脂类代谢及葡萄糖代谢对体重的影响。方法检测SIVmac239感染北平顶猴急性期炎症因子(TNF-α、IL-6)、脂类代谢(胆固醇、三酰甘油、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇)及葡萄糖代谢参数(胰岛素、胰岛素抵抗指数),比较体重增加组和体重减少组SIV感染北平顶猴之间的差异,运用Pearson相关分析探讨胰岛素抵抗与血浆病毒载量的相关性。结果在SIVmac239感染北平顶猴急性期,炎症因子和血脂四项在体重增加组与体重减少组之间无明显差异;体重增加组胰岛素水平明显下降,体重减少组胰岛素水平明显升高,并出现胰岛素抵抗表现;Pearson分析显示,感染后第5周及第11周胰岛素抵抗指数变化与血浆病毒载量呈正相关。结论 SIVmac239感染急性期,葡萄糖代谢异常可能是导致北平顶猴体重变化的主要原因。

关键词：艾滋病 SIVmac239 北平顶猴体重胰岛素抵抗

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