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

J Acquir Immune Defic Syndr. 2000 Sep 1;25(1):1-10. doi: 10.1097/00042560-200009010-00001.


Some colonic and neuronal cells which are CD4- but galactosyl ceramide-positive are susceptible to infection with HIV-1. We have previously shown that the T-cell tropic V3 loop of HIV-1 gp120 serves as a primary viral determinant for infectivity of CD4- neuronal cells. However, the nature of the V3 loop of HIV-1 needed for infection and the V3 loop's interaction with coreceptors 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 critical for HIV-1 infection of colonic HT-29 epithelial cells. Because T-cell tropic HIV-1 can use CXCR4 as a coreceptor in T cells, we set out to determine the role of CXCR4 during infection of HT-29 cells. Using reverse transcriptase-polymerase chain reaction (RT-PCR) and immunostaining, we show that these epithelial cells of colonic origin express the chemokine receptor CXCR4. Importantly, antibody against CXCR4 or a neutralizing antibody against HIV-1 gp120 V3 loop blocks T-cell tropic HIV-1 entry into HT-29 cells. These data indicate that the V3 loop of HIV-1 and the chemokine receptor CXCR4 are both critical for HIV-1 infection of colonic HT-29 epithelial cells. An HIV-1 T-tropic virus may be responsible for the infection of human colonic epithelial cells in vivo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Antibodies, Monoclonal / immunology
  • Cloning, Molecular
  • Consensus Sequence
  • Genes, Viral
  • HIV Envelope Protein gp120 / genetics*
  • HIV Envelope Protein gp120 / metabolism
  • HIV-1 / chemistry
  • HIV-1 / genetics*
  • HIV-1 / metabolism
  • HT29 Cells
  • Humans
  • Immunohistochemistry
  • Molecular Sequence Data
  • Neutralization Tests
  • Point Mutation
  • Receptors, CXCR4 / analysis*
  • Receptors, CXCR4 / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / virology*


  • Antibodies, Monoclonal
  • HIV Envelope Protein gp120
  • Receptors, CXCR4