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J. Exp. Med.,
Volume 188, Number 11, December 7, 1998 2113-2125
By

From the * Program in Molecular Medicine, University of Massachusetts Medical Center, Worcester,
Massachusetts 01605; and the After interaction of human immunodeficiency virus type 1 (HIV-1) virions with cell surface
receptors, a series of poorly characterized events results in establishment of a viral reverse transcription complex in the host cell cytoplasm. This process is coordinated in such a way that reverse transcription is initiated shortly after formation of the viral reverse transcription complex.
However, the mechanism through which virus entry and initiation of reverse transcription are
coordinated and how these events are compartmentalized in the infected cell are not known. In
this study, we demonstrate that viral reverse transcription complexes associate rapidly with the
host cell cytoskeleton during HIV-1 infection and that reverse transcription occurs almost entirely in the cytoskeletal compartment. Interruption of actin polymerization before virus infection reduced association of viral reverse transcription complexes with the cytoskeleton. In addition, efficient reverse transcription was dependent on intact actin microfilaments. The
localization of reverse transcription to actin microfilaments was mediated by the interaction of
a reverse transcription complex component (gag MA) with actin but not vimentin (intermediate filaments) or tubulin (microtubules). In addition, fusion, but not endocytosis-mediated HIV-1 infectivity, was impaired when actin depolymerizing agents were added to target cells
before infection but not when added after infection. These results point to a previously unsuspected role for the host cell cytoskeleton in HIV-1 entry and suggest that components of the
cytoskeleton promote establishment of the reverse transcription complex in the host cell and
also the process of reverse transcription within this complex.
D.I. Ivanovsky Institute of Virology, Academy of Medical Science,
Moscow 123098, Russia
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