Abstract
Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) is one of the common causes of cognitive dysfunction and morbidity among infected patients. However, to date, it remains unknown if a transmitted/founder (T/F) HIV-1 leads to neurological disorders during acute phase of infection. Since it is impossible to answer this question in humans, we studied NOD.Cg-Prkdc scid Il2rgtm1Wjl/SzJ mice (NSG) reconstituted with human PBMC (NSG-HuPBL), followed by the peritoneal challenge with the chronic HIV-1JR-FL and the T/F HIV-1BJZS7, respectively. By measuring viral load, P24 antigenemia and P24+ cells in peripheral blood and various tissue compartments, we found that systemic infections were rapidly established in NSG-HuPBL mice by both HIV-1 strains. Although comparable peripheral viral loads were detected during acute infection, the T/F virus appeared to cause less CD4+ T cell loss and less numbers of infected cells in different organs and tissue compartments. Both viruses, however, invaded brains with P24+/CD3+ T cells detected primarily in meninges, cerebral cortex and perivascular areas. Critically, brain infections with HIV-1JR-FL but not with HIV-1BJZS7 resulted in damaged neurons together with activated microgliosis and astrocytosis as determined by significantly increased numbers of Iba1+ microglial cells and GFAP+ astrocytes, respectively. The increased Iba1+ microglia was correlated positively with levels of P24 antigenemia and negatively with numbers of NeuN+ neurons in brains of infected animals. Our findings, therefore, indicate the establishment of two useful NSG-HuPBL models, which may facilitate future investigation of mechanisms underlying HIV-1-induced microgliosis and astrocytosis.
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Acknowledgments
The authors would like to thank Hong Kong Council for the AIDS Trust Fund (MSS 227R) for financial support on neuroAIDS research. We also thank Hong Kong Research Grant Council HKU5/CRF/13G to study T cell mechanism and China’s 12th 5-year National Science and Technology Mega Project 2013ZX10001005002001 as well as the University Development Fund of the University of Hong Kong and Li Ka Shing Faculty of Medicine Matching Fund to HKU AIDS Institute.
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Wu, X., Liu, L., Cheung, Kw. et al. Brain Invasion by CD4+ T Cells Infected with a Transmitted/Founder HIV-1BJZS7 During Acute Stage in Humanized Mice. J Neuroimmune Pharmacol 11, 572–583 (2016). https://doi.org/10.1007/s11481-016-9654-0
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DOI: https://doi.org/10.1007/s11481-016-9654-0