Document 0103
 DOCN  M9460103
 TI    Differences in CD4 dependence for infectivity of laboratory-adapted and
       primary patient isolates of human immunodeficiency virus type 1.
 DT    9404
 AU    Kabat D; Kozak SL; Wehrly K; Chesebro B; Department of Biochemistry and
       Molecular Biology, Oregon Health; Sciences University, Portland
       97201-3098.
 SO    J Virol. 1994 Apr;68(4):2570-7. Unique Identifier : AIDSLINE
       MED/94187098
 AB    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.
 DE    *Adaptation, Biological  Adsorption  Antigens,
       CD4/GENETICS/*PHARMACOLOGY  Comparative Study  Dose-Response
       Relationship, Drug  Hela Cells  Human  HIV-1/*GROWTH &
       DEVELOPMENT/ISOLATION & PURIF  Leukocytes, Mononuclear/MICROBIOLOGY
       Selection (Genetics)  Serial Passage  Support, U.S. Gov't, P.H.S.  Virus
       Cultivation/METHODS  Virus Replication/DRUG EFFECTS  JOURNAL ARTICLE

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       protected by Copyright Law (Title 17, U.S.Code).