Chakrabarti Ayan K, Caruso Lori, Ding Ming, Shen Chengli, Buchanan William, Gupta Phalguni, Rinaldo Charles R, Chen Yue
Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
AIDS Res Ther. 2009 Oct 2;6:20. doi: 10.1186/1742-6405-6-20.
HIV-1 infects gut associated lymphoid tissues (GALT) very early after transmission by multiple routes. The infected GALT consequently serves as the major reservoir for HIV-1 infection and could constantly shed HIV-1 and CD4+ T cells into the intestinal lumen. To examine this hypothesis, we monitored HIV-1 RNA/DNA and CD4 mRNA in fecal samples of chronically infected subjects with and without antiretroviral therapy (ART). We compared this to levels of HIV-1 RNA/DNA in urine and blood from the same subjects. Our results show that HIV-1 DNA, RNA and CD4 mRNA were detected in 8%, 19% and 31% respectively, of feces samples from infected subjects with detectable plasma viral load, and were not detected in any of subjects on ART with undetectable plasma viral load. In urine samples, HIV-1 DNA was detected in 24% of infected subjects with detectable plasma viral load and 23% of subjects on ART with undetectable plasma viral load. Phylogenetic analysis of the envelope sequences of HIV-1 revealed distinct virus populations in concurrently collected serum, feces and urine samples from one subject. In addition, our study demonstrated for the first time the presence of CD4 mRNA in fecal specimens of HIV-1 infected subjects, which could be used to assess GALT pathogenesis in HIV-1 infection.
HIV-1通过多种途径传播后，会在极早期感染肠道相关淋巴组织（GALT）。受感染的GALT因此成为HIV-1感染的主要储存库，并可能持续向肠腔释放HIV-1和CD4+T细胞。为了验证这一假设，我们监测了接受和未接受抗逆转录病毒疗法（ART）的慢性感染受试者粪便样本中的HIV-1 RNA/DNA和CD4 mRNA。我们将此与同一受试者尿液和血液中的HIV-1 RNA/DNA水平进行了比较。我们的结果表明，在血浆病毒载量可检测的感染受试者的粪便样本中，分别有8%、19%和31%检测到HIV-1 DNA、RNA和CD4 mRNA，而在血浆病毒载量不可检测的接受ART治疗的受试者中，均未检测到。在尿液样本中，在血浆病毒载量可检测的感染受试者中有24%检测到HIV-1 DNA，在血浆病毒载量不可检测的接受ART治疗的受试者中有23%检测到。对一名受试者同时采集的血清、粪便和尿液样本中HIV-1包膜序列的系统发育分析揭示了不同的病毒群体。此外，我们的研究首次证明了HIV-1感染受试者粪便标本中存在CD4 mRNA，这可用于评估HIV-1感染中的GALT发病机制。
