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.

Epithelial cells in human cervical and colonic mucosa do not express HIV receptor. However, HIV transmission occurs across the unbreached epithelia by an unknown mechanism. In this study, the effect of HIV exposure on tight junction and cytokine production in ectocervical and colon mucosal epithelia in tissue biopsies was investigated in an organ culture model. After HIV exposure, the distribution patterns and quantities of epithelial tight junction and adherens proteins were evaluated by immunofluorescence staining followed by confocal microscopy. Cytokine mRNA in the mucosal epithelia was also evaluated by real time RT-PCR. HIV transmission was evaluated by measuring p24 production in culture supernatant. Our results showed there were no significant changes in the distribution and quantities of epithelial tight junction/adherens junction proteins after exposure to HIV. However, higher levels of CXCL10 and CXCL11 mRNA expression were detected in HIV exposed ectocervical epithelia. In case of colon mucosa, higher levels of CXCL10 and IL6 mRNA expression were detected in HIV exposed colon mucosa. Our study suggests that HIV induces cytokine production in epithelial cells, which may facilitate HIV transmission by recruiting HIV target cells in the submucosal region. Furthermore, HIV transmission may not occur through epithelial tight junction/adherens junction disruption.

A vaccine-induced cellular immune response to simian immunodeficiency virus (SIV) in the gut mucosal tissue may prevent the establishment or severity of new SIV infection. An oral Clostridium perfringens expressing SIV p27 (Cpp27) vaccine that delivers SIV p27 to the gut was evaluated for its ability to prime multifunctional cellular immunity in the gut mucosa. Gut Peyers patches dendritic cells matured in response to in vitro exposure to Cp-p27 and stimulated production of p27-specific IFN-γ. In mice, the oral vaccination with the Cp-p27 vaccine and systemic immunization with adenovirus expressing SIV p27 (Ad-p27) induced robust systemic and mucosal immune responses. Furthermore, the prime-boost regimen induced p27-specific multifunctional CD8+ T cells in the gut. These results indicate that priming gut tissue with Cp-p27 can enhance the gut mucosal cellular immune response generated via systemic immunization with Adp27.