Abstract
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.
Highlights
Gut-Associated Lymphoid Tissues (GALT) are very important in HIV pathogenesis
Evaluation of the sensitivity of the PCR detection of HIV-1 DNA/RNA in human feces To test the sensitivity of amplifying HIV-1 DNA, 200 mg of normal donor fecal sample was mixed with different concentrations of HIV-1 positive 8E5 cells
HIV-1 DNA was detected from the DNA isolated from normal donor feces mixed with 8E5 cells and the detection limit was as low as 2.5 copies/reaction
Summary
Gut-Associated Lymphoid Tissues (GALT) are very important in HIV pathogenesis. GALT is the largest single immunologic organ in the body, containing a large amount of lymphocytes. Contrast to the blood and other organized lymphoid tissues, which contain abundance of naive resting T cells, a majority of the CD4+ T cells that reside in GALT are CCR5 positive, activated memory CD4 T cells which are the preferred target cells for HIV/SIV infection [1,2,3]. We hypothesize that during HIV-1 infection, HIV-1 free virus and infected/uninfected CD4+ T cells constantly shed from GALT into the intestinal lumen and are discharged with feces. There is no information on HIV-1 detection in the feces of chronically infected subjects, especially in subjects undergoing antiretroviral drug therapy (ART). Feces could be an accessible, non-invasive and inexpensive specimen to assess CD4+ T cell depletion of GALT, since CD4+ T cells could shed into the intestinal lumen and be discharged in feces
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