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Analysis of immunoglobulin, complements and CRP levels in serum of captive northern pig-tailed macaques （Macaca leonina）

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Zoological Research 2014年第3期35卷 196-203页

作者： Xiao-Liang ZHANG Wei PANG De-Yao DENG Long-Bao LV Yue FENG Yong-Tang ZHENG Faculty of Life Science and Technology Kunming University of Science and Technology Kunming Yunnan 650500 China Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province Kunming Institute of Zoology Chinese Academy of Sciences Kunming Yunnan 650223 China Department of Clinical Laboratory the Second Hospital of Yunnan Province Kunming Yunnan 650021 China Kunming Primate Research Center Kunming Institute of Zoology Chinese Academy of Sciences Kunming Yunnan 650223 China

The northem pig-tailed macaque （NPM, Macaca leonina） has become a widely used animal model in biomedical research. In this study, we measured serum immunoglobulin IgG, IgM, IgA, complement C3, C4 and CRP levels in 3-11 year old captive northem pig-tailed macaques using HITACHI 7600-20 automated chemistry analyzer in order to determine the influences of age and gender on these items. The results showed that serum IgA, IgM, C3 and C4 levels were not correlated with age （P〉0.05）, while serum IgG levels increased progressively with age （r=0.202; P=0.045）. Serum IgG, IgA, IgM and C3 levels were higher in females than in males （P〈0.05）. Moreover, serum C3 concentration was both positively and strongly correlated with that of C4 （r=0.700; P〈0.0001）. This study provides basic serum immunoglobulin and complement data of captive northem pig-tailed macaques, which may prove useful for future breeding efforts and biomedical research.

关键词： Northern pig-tailed macaque (Macaca leonina) Immunoglobulin Complement C-reactive protein

Molecular cloning and anti-HIV-1 activities of APOBEC3s from northern pig-tailed macaques(Macaca leonina)

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Zoological Research 2016年第4期37卷 246-251页

作者： Xiao-Liang ZHANG Jia-Hao SONG Wei PANG Yong-Tang ZHENG Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province Kunming Institute of Zoology Chinese Academy of Sciences Faculty of Life Science and Technology Kunming University of Science and Technology Institute of Health Sciences Anhui University Kunming Primate Research Center of the Chinese Academy of Sciences Kunming Institute of Zoology Chinese Academy of Sciences

Northern pig-tailed macaques （NPMs, Macaca leonina） are susceptible to HIV-1 infection largely due to the loss of HIV-l-restricting factor TRIM5a. However, great impediments still exist in the persistent replication of HIV-1 in vivo, suggesting some viral restriction factors are reserved in this host The APOBEC3 proteins have demonstrated a capacity to restrict HIV-1 replication, but their inhibitory effects in NPMs remain elusive. In this study, we cloned the NPM A3A-A3H genes, and determined by BLAST searching that their coding sequences （CDSs） showed 99% identity to the corresponding counterparts from rhesus and southern pig-tailed macaques. We further analyzed the anti-HIV-1 activities of the A3A-A3H genes, and found that A3G and A3F had the greatest anti-HIV-1 activity compared with that of other members. The results of this study indicate that A3G and A3F might play critical roles in limiting HIV-1 replication in NPMs in vivo. Furthermore, this research provides valuable information for the optimization of monkey models of HIV-1 infection.

关键词： Macaca leonina Northern pig-tailed macaques APOBEC3 HIV-1

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

Flow cytometric characterizations of leukocyte subpopulations in the peripheral blood of northern pig-tailed macaques （Macaca leonina）

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Zoological Research 2014年第6期35卷 465-473页

作者： Hong-Yi ZHENG Ming-Xu ZHANG Lin-Tao ZHANG Xiao-Liang ZHANG Wei PANG Long-Bao LYu Yong-Tang ZHENG Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province Kunming Institute of Zoology Chinese Academy of Sciences Kunming Yunnan 650223 China School of Life Sciences University of Science and Technology of China Hefei Anhui 230026 China Kunming College of Life Science University of Chinese Academy of Sciences Kunming Yunnan 650204 China Faculty of Life Science and Technology Kunming University of Science and Technology Kunming Yunnan 650500 China Kunming Primate Research Center Kunming Institute of Zoology Chinese Academy of Sciences Kunming Yunnan 650223 China

Pig-tailed macaques(Macaca nemistrina group) have been extensively used as non-human primate animal models for various human diseases in recent years, notably for AIDS research due to their sensitivity to HIV-1. Northern pig-tailed macaques(M. leonina) are distributed in China and other surrounding Southeast Asia countries. Although northern pig-tailed macaques have been bred on a large scale as experimental animals since 2012, the reference value of normal levels of leukocytes is not available. To obtain such information, 62 blood samples from male and female healthy northern pig-tailed macaques at different ages were collected. The normal range of major leukocyte subpopulations, such as T lymphocytes, B lymphocytes, natural killer(NK) cells, monocytes, and the expression levels of activation or differentiation related molecules(CD38, HLA-DR, CCR5, CD21, IgD, CD80 and CD86) on lymphocytes were analyzed by flow cytometry. The counts of B cells decreased with age, but those of CD8+ T cells and NK cells and the frequency of CD38+HLA-DR+CD4+ T cells were positively correlated with age. The counts of leukocyte subpopulations were higher in males than those in females except for CD4+ T cells. Males also showed higher expression levels of Ig D and CD21 within B cells. This study provides basic data about the leukocyte subpopulations of northern pig-tailed macaques and compares this species with commonly used Chinese rhesus macaques(M. mulatta), which is meaningful for the biomedical application of northern pig-tailed macaques.

关键词：流式细胞仪分析细胞亚群猕猴酒店外周血 T淋巴细胞生物医学应用女性健康

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

HIV-1 can infect northern pig-tailed macaques(Macaca leonina) and form viral reservoirs in vivo

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Science Bulletin 2017年第19期62卷 1315-1324页

作者： Wei Pang Gao-Hong Zhang Jin Jiang Hong-Yi Zheng Lin-Tao Zhang Xiao-Liang Zhang Jia-Hao Song Ming-Xu Zhang Jia-Wu Zhu Ai-Hua Lei Ren-Rong Tian Xiao-Ming Liu Liguo Zhang Guangxia Gao Lishan Su Yong-Tang Zheng Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province Kunming Institute of ZoologyChinese Academy of Sciences university of Chinese Academy of Sciences Institute of Health Sciences Anhui University South China Institute of Endangered Animal Guandong Academy of Sciences Key Laboratory of Infection and Immunity Institute of BiophysicsChinese Academy of Sciences Department of Microbiology and Immunology School of MedicineThe University of North Carolina at Chapel Hill

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 ***, we inoculated 4 northern pig-tailed macaques(NPM) with the HIV-1 strain HIV-1_(NL4.3) 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-1could 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-log_(10) 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.

关键词： HIV-1 病毒库感染外周血单个核细胞猕猴体内北方猪

Inhibitory effects of chloroquine on the activation of plasmacytoid dendritic cells in SIVmac239-infected Chinese rhesus macaques

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Cellular & Molecular Immunology 2012年第5期9卷 410-416页

作者： Jian-Ping Ma Hou-Jun Xia Gao-Hong Zhang Jian-Bao Han Li-Guo Zhang Yong-Tang Zheng Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences&Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunmingChina Graduate university of the Chinese Academy of Sciences BeijingChina CAS Key Laboratory of Infection and Immunity Institute of BiophysicsChinese Academy of SciencesBeijingChina

It is currently widely accepted that immune activation in HIV-infected individuals leads to a severe loss of CD4＋ T cells and the progression to AIDS. However, the underlying mechanism of this immune activation remains unclear. Experimental data suggest that the activation of plasmacytoid dendritic cells （pDCs） by plasma viremia may play a critical role in HIV-induced immune activation. In this study, we found that the level of immune activation was higher in the late phase of SIVmac239 infection compared with chronic infection, which suggests that immune activation might be related to disease progression in SIVmac239-infected non-human primate models. Our work also showed that chloroquine could effectively inhibit the activation of pDCs in vitro and in vivo. However, chloroquine treatment of SIVmac239-infected macaques had no significant influence on the Cellular composition of peripheral blood in these animals.

关键词： Chinese rhesus macaque chloroquine immune activation pDC SIV

Replication potentials of HIV-1/HSIV in PBMCs from northern pigtailed macaque （Macaca leonina）

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Zoological Research 2014年第3期35卷 186-195页

作者： Ai-Hua LEI Gao-Hong ZHANG Ren-Rong TIAN Jia-Wu ZHu Hong-Yi ZHENG Wei PANG Yong-Tang ZHENG Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province Kunming Institute of Zoology Chinese Academy of Sciences Kunming 650223 China Kunming College of Life Sciences University of Chinese Academy of Sciences Kunming Yunnan 650204 China university of Science and Technology of China Hefei 230026 China Kunming Primate Research Center Kunming Institute of Zoology Chinese Academy of Sciences Kunming 650223 China

The northern pig-tailed macaque （Macaca leonina） has been identified as an independent species of Old World monkey, and we previously found that PBMCs from M. leonina were susceptible to human immunodeficiency virus type 1 （HIV-1）, which may be due to the absence of a TRIM5 protein restricting HIV-1 replication. Here we investigated the infection potentials of six laboratory adapted HIV-1 strains and three primary HIV-1 isolates in PBMCs from M. leonina. The results indicate that these strains are characterized by various but low replication levels, and among which, HIV-INL4-3 shows the highest replication ability. Based on the abundant evidence of species-specific interactions between restriction factors APOBEC3 and HIV/SIV-derived Vif protein, we subsequently examined the replication potentials of v/f-substituted HIV-1 （HSIV） in M. leonina PBMCs. Notably, HSIV-vifmac and stHIV-lsv chimeras, two HIV-1Ni.4-3-derived viruses encoding the viral infectivity factor （Vif） protein from SIVmac239, replicated robustly in cells from M. leonina, which suggests that HSIV could effectively antagonize the antiviral activity of APOBEC3 proteins expressed in cells of M. leonina. Therefore, our data demonstrate that M. leonina has the potential to be developed into a promising animal model for human AIDS.

关键词： HIV-1 HSIV Replication PBMC Northern pig-tailed macaque (Macaca leonina)

TRIM5α分子结构和限制HIV-1复制机制的研究进展

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病毒学报 2009年第2期25卷 148-153页

作者：汤霞况轶群郑永唐中国科学院昆明动物研究所动物模型和人类疾病机理重点实验室分子免疫药理学实验室云南昆明650223 中国科学院研究生院北京100039

TRIM(Tripartite motif protein)家族蛋白,又称为三重基序蛋白,它们均含有RING、B-box和Coiled-Ciol三个结构域。TRIM家族蛋白广泛分布于各种哺乳动物细胞中,具有众多功能,与细胞的分裂、生长、分化和成熟都有密切关系。TRIM家族成员之... 详细信息

TRIM(Tripartite motif protein)家族蛋白,又称为三重基序蛋白,它们均含有RING、B-box和Coiled-Ciol三个结构域。TRIM家族蛋白广泛分布于各种哺乳动物细胞中,具有众多功能,与细胞的分裂、生长、分化和成熟都有密切关系。TRIM家族成员之一TRIM5α是哺乳动物细胞中一种重要的限制因子,它们以一种物种依赖的方式限制包括HIV-1(Human immunodeficiency virustype1)在内的多种逆转录病毒复制。自2004年Stremlau M和Nisole S等分别发现恒河猴TRIM5α和鹰猴TRIMCyp能强烈限制HIV-1复制以来,[第一段]

关键词： TRIM5α CypA HIV-1 灵长类动物