The Establishment of an In Vivo HIV-1 Infection Model in Humanized B-NSG Mice
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RESEARCH ARTICLE
The Establishment of an In Vivo HIV-1 Infection Model in Humanized B-NSG Mice Tian-Jiao Fan1,2 • Li Sun1 • Xian-Guang Yang3 • Xia Jin1 • Wei-Wei Sun1,2
•
Jian-Hua Wang1,2
Received: 12 July 2019 / Accepted: 2 December 2019 Ó Wuhan Institute of Virology, CAS 2019
Abstract Suitable animal models for human immunodeficiency virus type 1 (HIV-1) infection are important for elucidating viral pathogenesis and evaluating antiviral strategies in vivo. The B-NSG (NOD-PrkdcscidIl2rgtm1/Bcge) mice that have severe immune defect phenotype are examined for the suitability of such a model in this study. Human peripheral blood mononuclear cells (PBMCs) were engrafted into B-NSG mice via mouse tail vein injection, and the repopulated human T-lymphocytes were observed at as early as 3-weeks post-transplantation in mouse peripheral blood and several tissues. The humanized mice could be infected by HIV-1, and the infection recapitulated features of T-lymphocyte dynamic observed in HIV-1 infected humans, meanwhile the administration of combination antiretroviral therapy (cART) suppressed viral replication and restored T lymphocyte abnormalities. The establishment of HIV-1 infected humanized B-NSG mice not only provides a model to study virus and T cell interplays, but also can be a useful tool to evaluate antiviral strategies. Keywords Human immunodeficiency virus type 1 (HIV-1) Animal model Acute infection B-NSG mice
Introduction Suitable human immunodeficiency virus type 1 (HIV-1) infected animal models assist the elucidation of viral pathogenesis and the evaluation of antiviral strategies. Currently, several models based on nonhuman primates (NHP) or humanized mice are available (Kumar et al. 2016). These NHPs, including Northern pig-tailed macaque (Macaca nemestrina) and Indian Rhesus monkey (Macaca mulatta), have been used to establish the acutely and
Tian-Jiao Fan and Li Sun have contributed equally to this work. & Wei-Wei Sun [email protected] & Jian-Hua Wang [email protected] 1
CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China
2
University of Chinese Academy of Sciences, Beijing 100039, China
3
College of Life Science, Henan Normal University, Xinxiang 453007, China
persistently viral infection models by infection with simian immunodeficiency virus (SIV) or chimeric simian/human immunodeficiency virus (SHIV). These models are useful for studying viral transmission, pathogenesis, drugs, antibodies and candidate vaccines (Dinoso et al. 2009; Kline et al. 2013; Hessell and Haigwood 2015). Meanwhile, these models have several noted limitations, such as the inability to precisely examine human specific immune functions because of genetic differences in major histocompatibility complex (MHC) genes, the difficulty to operate sufficient sample size due to their expensive costs, and the mounting ethical concerns of experimentation wi
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