Primary intestinal epithelial cells selectively transfer R5 HIV-1 to CCR5+ cells

Nat Med. 2002 Feb;8(2):150-6. doi: 10.1038/nm0202-150.


The upper gastrointestinal tract is a principal route of HIV-1 entry in vertical transmission and after oral-genital contact. The phenotype of the newly acquired virus is predominantly R5 (CCR5-tropic) and not X4 (CXCR4-tropic), although both R5 and X4 viruses are frequently inoculated onto the mucosa. Here we show that primary intestinal (jejunal) epithelial cells express galactosylceramide, an alternative primary receptor for HIV-1, and CCR5 but not CXCR4. Moreover, we show that intestinal epithelial cells transfer R5, but not X4, viruses to CCR5+ indicator cells, which can efficiently replicate and amplify virus expression. Transfer was remarkably efficient and was not inhibited by the fusion blocker T-20, but was substantially reduced by colchicine and low (4 degrees C) temperature, suggesting endocytotic uptake and microtubule-dependent transcytosis of HIV-1. Our finding that CCR5+ intestinal epithelial cells select and transfer exclusively R5 viruses indicates a mechanism for the selective transmission of R5 HIV-1 in primary infection acquired through the upper gastrointestinal tract.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Anti-HIV Agents / chemistry
  • HIV Envelope Protein gp41 / chemistry
  • HIV Envelope Protein gp41 / genetics
  • HIV Infections / immunology*
  • HIV Infections / transmission
  • HIV-1 / physiology*
  • Humans
  • Immunity, Mucosal
  • Infectious Disease Transmission, Vertical
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / virology*
  • Jejunum
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics
  • Receptors, CCR5 / chemistry
  • Receptors, CCR5 / immunology*
  • Receptors, HIV / immunology*
  • Sequence Alignment
  • Sequence Homology, Amino Acid


  • Anti-HIV Agents
  • HIV Envelope Protein gp41
  • Peptide Fragments
  • Receptors, CCR5
  • Receptors, HIV
  • peptide N36