Genetic determinants controlling HIV-1 tropism for CD4-/GalCer+ human intestinal epithelial cells

Nouara Yahi, Lee Ratner, Janet M. Harouse, Francisco González-Scarano, Jacques Fantini

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

It is now well-established that some viruses, including adenovirus and Herpes simplex virus, can recognize more than one receptor. The human immunodeficiency virus type 1 (HIV-1) recognizes both the CD4 glycoprotein on the surface of CD4+ lymphocytes and macrophages, and the glycosphingolipid galactosylceramide (GalCer) on cells of neural and intestinal origin. The infection of the CD4-/ GalCer- HT-29 intestinal epithelial cell line is restricted to a subset of T-cell-line-tropic isolates. The determinants responsible for HIV-1 infection of HT-29 cells have been characterized by functional analysis of chimeric proviral clones derived from T-cell-line-tropic (HXB2) and macrophage-tropic isolates (ADA, YU2, and 89.6, respectively). Replacement of the HXB2 V3-loop sequence with that derived from either ADA or YU2 resulted in a virus that could no longer infect HT-29 cells. However, the reciprocal replacement of ADA or YU2 V3-loop by the corresponding HXB2 sequence did not confer the ability to infect HT-29 cells. By contrast, insertion in the 89.6-sequence of a 193-amino-acid fragment from the envelope region of HXB2 containing the V3, V4 and V5 regions resulted in a virus able to infect HT-29. Moreover, recombinant viruses that separate this 193-amino-acid fragment into two distinct chimeras were each able to confer the infection phenotype. Taken together, these data emphasize the importance of the V3 loop in the tropism of HIV-1 for CD4-/GalCer+ intestinal cells. In addition, the conformation of the V3 loop that is operative for GalCer recognition may be modulated by distinct domains of the gp120 molecule.

Original languageEnglish (US)
Pages (from-to)161-168
Number of pages8
JournalPerspectives in Drug Discovery and Design
Volume5
DOIs
StatePublished - Jan 1 1996

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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