AIDS research and human retroviruses 2018 04 10() doi 10.1089/AID.2017.0249
Ex vivo mucosal explants have become a mainstay of HIV-1 studies using human tissue. Here we examine the baseline phenotypic and virologic differences between biopsies derived from the small and large intestine for use in ex vivo explant studies. To do this, we collected endoscopic mucosal biopsies from both small intestine (SI) and large intestine (LI) from the same healthy, HIV-seronegative participants. Mucosal mononuclear cell phenotypes and quantity were compared using flow cytometry. Comparative HIV-1 infectibility of the explants was assessed using an ex vivo explant HIV-1 infection assay. We found that all biopsies had similar numbers of T cells per biopsy. While the percentage of CD4+ T cells from SI biopsies expressed significantly more activation markers (CD38, HLA-DR) and HIV co-receptors (CXCR4, CCR5), the absolute numbers of activated CD4+ T cells was similar between both sites. LI explants, however, supported more efficient HIV-1 infection, as evidenced by earlier rise in p24 accumulation and greater percent of infected explants at limiting infectious doses. These results suggest that explants from LI biopsies support more efficient HIV-1 infection than SI biopsies, despite similar numbers of available, activated HIV-1 target cells. These findings highlight important differences in LI and SI explants which must be considered in designing and interpreting ex vivo HIV-1 infection studies, and suggest that factors within the tissue other than target cell number and activation state may play a role in regulating HIV-1 infection.