Pang Wei, Zhang Gao-Hong, Jiang Jin, Zheng Hong-Yi, Zhang Lin-Tao, Zhang Xiao-Liang, Song Jia-Hao, Zhang Ming-Xu, Zhu Jia-Wu, Lei Ai-Hua, Tian Ren-Rong, Liu Xiao-Ming, Zhang Liguo, Gao Guangxia, Su Lishan, Zheng Yong-Tang
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 Zoology, Chinese Academy of Sciences, Kunming 650223, China.
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 Zoology, Chinese Academy of Sciences, Kunming 650223, China; University of Chinese Academy of Sciences, Beijing 100091, China.
Sci Bull (Beijing). 2017 Oct 15;62(19):1315-1324. doi: 10.1016/j.scib.2017.09.020. Epub 2017 Sep 28.
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-1 and monitored the infection for approximately 3years (150weeks). The HIV-1-infected NPMs showed transient viremia for about 10weeks after infection. However, cell-associated proviral DNA and viral RNA persisted in the peripheral blood and lymphoid organs for about 3years. 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-log 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 asa potential model for HIV-1 reservoir research.
HIV-1的病毒储存库是治愈艾滋病的主要障碍。能够直接感染HIV-1的新型动物模型将有助于制定根除感染的有效策略。在此,我们用HIV-1毒株HIV-1接种了4只北方豚尾猕猴(NPM),并对感染情况进行了约3年(150周)的监测。感染HIV-1的NPM在感染后约10周出现短暂病毒血症。然而,细胞相关的前病毒DNA和病毒RNA在外周血和淋巴器官中持续存在约3年。此外,在长期感染期间,可从外周血单个核细胞(PBMC)中成功分离出具有复制能力的HIV-1。携带前病毒的HIV-1感染NPM中静息CD4 T细胞的数量每百万细胞下降2至3个对数,并且这些前病毒在体外和体内均可因潜伏逆转剂JQ1和原卟啉的共刺激而重新激活。我们的结果表明,NPM可被HIV-1感染,并在NPM中形成长期病毒储存库,这可能作为HIV-1储存库研究的潜在模型。