Establishment of a functional human immunodeficiency virus type 1 (HIV- 1) reverse transcription complex involves the cytoskeleton

Alissa Bukrinskaya, Beda Brichacek, Angela Mann, Mario Stevenson

Research output: Contribution to journalArticle

218 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2113-2125
Number of pages13
JournalJournal of Experimental Medicine
Volume188
Issue number11
DOIs
StatePublished - Dec 7 1998

Keywords

  • Cytoskeleton
  • HIV-1 entry
  • Reverse transcription

ASJC Scopus subject areas

  • Immunology

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