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

Summary

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.

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Correspondence to Nouara Yahi.

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Yahi, N., Ratner, L., Harouse, J.M. et al. Genetic determinants controlling HIV-1 tropism for CD4/GalCer+ human intestinal epithelial cells. Perspectives in Drug Discovery and Design 5, 161–168 (1996). https://doi.org/10.1007/BF02174011

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Keywords

  • Herpes Simplex
  • Intestinal Epithelial Cell
  • Human Intestinal Epithelial Cell
  • Intestinal Epithelial Cell Line
  • Intestinal Origin