Differences in CD4 dependence for infectivity of laboratory-adapted and primary patient isolates of human immunodeficiency virus type 1

David Kabat, Susan L. Kozak, Kathy Wehrly, Bruce Chesebro

Research output: Contribution to journalArticlepeer-review

131 Scopus citations

Abstract

CD4 is known to be an important receptor for human immunodeficiency virus type 1 (HIV-1) infection of T lymphocytes and macrophages. However, the limiting steps in CD4-dependent HIV-1 infections in vivo and in vitro are poorly understood. To address this issue, we produced a panel of HeLa-CD4 cell clones that express widely different amounts of CD4 and quantitatively analyzed their infection by laboratory-adapted and primary patient HIV-1 isolates. For all HIV-1 isolates, adsorption from the medium onto HeLa-CD4 cells was inefficient and appeared to be limiting for infection in the conditions of our assays. Adsorption of HIV-1 onto CD4-positive peripheral blood mononuclear cells was also inefficient. Moreover, there was a striking difference between laboratory-adapted and primary T-cell-tropic HIV-1 isolates in the infectivity titers detected on different HeLa-CD4 cells. Laboratory-adapted HIV-1 isolates infected all HeLa-CD4 cell clones with equal efficiencies regardless of the levels of CD4, whereas primary HIV-1 isolates infected these clones in direct proportion to cellular CD4 expression. Our interpretation is that for laboratory-adapted isolates, a barrier step that preceeds CD4 encounter was limiting and the subsequent CD4- dependent virus capture process was highly efficient, even at very low cell surface concentrations. In contrast, for primary HIV-1 isolates, the CD4- dependent steps appeared to be much less efficient. We conclude that primary isolates of HIV-1 infect inefficiently following contact with surfaces of CD4-positive cells, and we propose that this confers a selective disadvantage during passage in rapidly dividing leukemia cell lines. Conversely, in vivo selective pressure appears to favor HIV-1 strains that require large amounts of CD4 for infection.

Original languageEnglish (US)
Pages (from-to)2570-2577
Number of pages8
JournalJournal of virology
Volume68
Issue number4
DOIs
StatePublished - Apr 1994

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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