T-tropic sequence of the V3 loop is critical for HIV-1 infection of CXCR4-positive colonic HT-29 epithelial cells

Some colonic and neuronal cells which are CD4(-) but galactosyl ceramide-po sitive are susceptible to infection with HIV-1. We have previously shown th at the T-cell tropic V3 loop of HIV-1 gp120 serves as a primary viral deter minant for infectivity of CD4- neuronal cells. However, the nature of the V 3 loop of HIV-1 needed for infection and the V3 loop's interaction with cor eceptors on colonic epithelial cells have not been fully analyzed. By using HIV-1 molecular clones, we show that the T-cell tropic V3 domain is critic al for HIV-1 infection of colonic HT-29 epithelial cells. Because T-cell tr opic HIV-1 can use CXCR4 as a coreceptor in T cells, we set out to determin e the role of CXCR4 during infection of HT-29 cells. Using reverse transcri ptase-polymerase chain reaction (RT-PCR) and immunostaining, we show that t hese epithelial cells of colonic origin express the chemokine receptor CXCR 4. Importantly, antibody against CXCR4 or a neutralizing antibody against H IV-1 gp120 V3 loop blocks T-cell tropic HIV-1 entry into MT-29 cells. These data indicate that the V3 loop of HIV-1 and the chemokine receptor CXCR4 a re both critical for HIV-1 infection of colonic MT-29 epithelial cells. An HIV-1 T-tropic virus may be responsible for the infection of human colonic epithelial cells in vivo.