期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2005
卷号：102
期号：22
页码：8000-8005
DOI：10.1073/pnas.0503233102
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Unlike HIV-1 and simian immunodeficiency virus (SIV), which induce a slow, unrelenting loss of immune function spanning several years, highly pathogenic simian-human immunodeficiency viruses (SHIVs) induce a rapid, complete, and irreversible depletion of CD4+ T lymphocytes in rhesus monkeys within weeks of infection, leading to death from immunodeficiency. We recently reported that, because these SHIVs exclusively use the CXCR4 coreceptor for cell entry, they target naive CD4+ T cells for depletion in infected monkeys, whereas SIVs, which use CCR5, not CXCR4, cause the selective loss of memory CD4+ T lymphocytes in vivo. Here we show both by DNA PCR analyses and infectivity assays, using live sorted CD4+ T lymphocyte subsets, that 30-90% of circulating naive cells were productively infected by day 10 after inoculation. This result implies that direct cell killing, not bystander apoptosis, is responsible for the massive loss of CD4+ T cells in the X4-tropic SHIV model. Furthermore, we directly demonstrate that >96% of virus producing cells did not express the Ki-67 proliferation marker on day 10 after inoculation using confocal microscopic analysis of lymph nodes samples. This finding is consistent with the prodigious levels of plasma viremia measured during acute X4-tropic SHIV infections of macaques being generated almost entirely by resting naive CD4+ T cells.
关键词：acute infection ; animal model ; CXCR4-tropic SHIV ; HIV pathogenesis
