In vitro differentiation of monocytoid THP-1 cells affects their permissiveness for HIV strains: a model system for studying the cellular basis of HIV differential tropism.

Abstract:

:The prototypic macrophage-tropic HIV-1 isolate, HIV-1BaL, cannot replicate in the monocytoid cell line THP-1. After induction of differentiation by a phorbol diester, a fraction of THP-1 cells became permissive to HIV-1BaL. In contrast, this treatment decreased permissiveness for the lymphotropic isolate HIV-1LAI. Viral DNA was not synthesized in unstimulated THP-1 cells, as determined with PCR, suggesting that the block to HIV-1BaL replication in these cells occurred at an early step of the virus replicative cycle prior to or at the level of reverse transcription. Virus binding studies showed that differences in cell permissiveness for HIV-1BaL were not due to altered virus binding. Substantial amounts of HIV-1BaL bound to both undifferentiated and differentiated THP-1 cells, and this binding could not be prevented by blocking with the anti-CD4 antibody Leu3a, which did prevent the binding of HIV-1LAI to CEM T lymphoid cells. While Leu3a was very effective at preventing the infection by HIV-1LAI in CEM cells, it was less effective in preventing HIV-1BaL infection of differentiated THP-1 cells or primary macrophages. Although it is likely that molecules other than CD4 on monocytic cells can mediate binding of macrophage-tropic HIV, the binding of HIV-1BaL to THP-1 cells was not sufficient for infection, because binding was the same in nonpermissive undifferentiated cells as in permissive differentiated cells. Thus, the restriction of viral replication in this model cell system occurs at some step after virion binding. Comparison of differentiated THP-1 cells with their undifferentiated counterparts may provide an approach to defining cellular determinants of HIV host range other than CD4 expression and to characterizing the incompletely defined steps of viral entry.

journal_name

Virology

journal_title

Virology

authors

Meylan PR,Spina CA,Richman DD,Kornbluth RS

doi

10.1006/viro.1993.1121

subject

Has Abstract

pub_date

1993-03-01 00:00:00

pages

256-67

issue

1

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(83)71121-9

journal_volume

193

pub_type

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