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

Academic Article

Abstract

  • 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 °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.
  • Published In

  • Nature Medicine  Journal
  • Digital Object Identifier (doi)

    Author List

  • Meng G; Wei X; Wu X; Sellers MT; Decker JM; Moldoveanu Z; Orenstein JM; Graham MF; Kappes JC; Mestecky J
  • Start Page

  • 150
  • End Page

  • 156
  • Volume

  • 8
  • Issue

  • 2