Replication of patient isolates of human immunodeficiency virus type 1 in T cells: a spectrum of rates and efficiencies of entry.
TL;DR: In this paper, the authors analyzed the replication of a "slow/low" isolate from the pre-AIDS period of infection and two "rapid/high" isolates from the AIDS period to determine which steps in the virus life cycle determine differences in the growth characteristics of patient isolates.
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Abstract: Isolates of human immunodeficiency virus type 1 (HIV-1) undergo many different rates of replication, with the time course of replication being determined by the host cell and the virus. Recently, we demonstrated that the permissiveness of four CD4+ T-cell lines for the laboratory strain NL4-3 correlated with the rate and efficiency of virus entry. In this study, we have analyzed the replication of a "slow/low" isolate from the pre-AIDS period of infection and two "rapid/high" isolates from the AIDS period of infection to determine which steps in the virus life cycle determine differences in the growth characteristics of patient isolates. Differences in the growth of the patient isolates correlated with differences in entry but not postentry steps of the virus life cycle. The two rapid/high patient isolates (SF33 and SF216) underwent 50% entry in less than or equal to 0.5 hr in C8166 cells, in less than or equal to 1 hr in mitogen-stimulated peripheral blood mononuclear cells, and in greater than or equal to 2.5 hr in H9 cells. In contrast, a class 3 slow/low patient isolate required 1 hr for 50% entry into C8166 cells, 3 hr for 50% entry into peripheral blood mononuclear cells, and 5-6 hr for 50% entry into H9 cells. Entry efficiency correlated with entry rate, with the rapid/high viruses having a 2-fold higher titer and the slow/low virus having a 5-fold higher titer on C8166 than H9 cells. The laboratory strain NL4-3 displayed intermediate rates and efficiencies of entry. These data demonstrate that entry characteristics are major determinants of the pathogenic potential of patient isolates.
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Citations
Cellular proteins bound to immunodeficiency viruses: implications for pathogenesis and vaccines.
Larry O. Arthur,Julian W. Bess,Raymond C. Sowder,Raoul E. Benveniste,Dean L. Mann,Jean-Claude Chermann,Louis E. Henderson +6 more
TL;DR: The specific, selective association of these cellular proteins in a physiologically relevant manner has major implications for the understanding of the infection process and the pathogenesis of immunodeficiency viruses and should be considered in the design of vaccines.
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Primary isolates of human immunodeficiency virus type 1 are relatively resistant to neutralization by monoclonal antibodies to gp120, and their neutralization is not predicted by studies with monomeric gp120.
John P. Moore,Yunzhen Cao,Limo Qing,Quentin J. Sattentau,J. Pyati,R. Koduri,James E. Robinson,Carlos F. Barbas,Dennis R. Burton,David D. Ho +9 more
TL;DR: The mechanism of resistance of primary isolates to most neutralizing antibodies is complex, and it is suggested that it involves an inaccessibility of antibody binding sites in the context of the native glycoprotein complex on the virion.
426
Differences in CD4 dependence for infectivity of laboratory-adapted and primary patient isolates of human immunodeficiency virus type 1.
TL;DR: It is concluded that primary isolates of HIV-1 infect inefficiently following contact with surfaces of CD4-positive cells, and it is proposed that this confers a selective disadvantage during passage in rapidly dividing leukemia cell lines.
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Molecular determinants of acute single-cell lysis by human immunodeficiency virus type 1.
TL;DR: It is suggested that intracellular envelope glycoprotein-CD4 interactions initiate autofusion events that disrupt cell membrane integrity, leading to single-cell lysis by HIV-1.
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Selective transmission of R5 HIV-1 variants: where is the gatekeeper?
TL;DR: It is proposed that the principle of multiple barriers is more general and not restricted to protection against X4 HIV-1 but rather can be applied to other phenomena when one factor has a selective advantage over the other(s).
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