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

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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
StatePublished - Apr 1994

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Human immunodeficiency virus 1
HIV-1
pathogenicity
HeLa Cells
infection
Clone Cells
Virus Diseases
cells
clones
Adsorption
adsorption
T-lymphocytes
Laboratory Infection
T-Lymphocytes
mononuclear leukocytes
Infection
leukemia
Blood Cells
tropics
Leukemia

ASJC Scopus subject areas

  • Immunology

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Differences in CD4 dependence for infectivity of laboratory-adapted and primary patient isolates of human immunodeficiency virus type 1. / Kabat, David; Kozak, Susan L.; Wehrly, Kathy; Chesebro, Bruce.

In: Journal of Virology, Vol. 68, No. 4, 04.1994, p. 2570-2577.

Research output: Contribution to journalArticle

Kabat, David ; Kozak, Susan L. ; Wehrly, Kathy ; Chesebro, Bruce. / Differences in CD4 dependence for infectivity of laboratory-adapted and primary patient isolates of human immunodeficiency virus type 1. In: Journal of Virology. 1994 ; Vol. 68, No. 4. pp. 2570-2577.
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