UMMS Affiliation
Program in Molecular Medicine
Publication Date
1998-12-08
Document Type
Article
Subjects
Cell Line; Cytoskeleton; HIV Infections; HIV Reverse Transcriptase; HIV-1; Humans; *Virus Replication
Disciplines
Cell and Developmental Biology | Immunology and Infectious Disease
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.
Source
J Exp Med. 1998 Dec 7;188(11):2113-25.
Journal/Book/Conference Title
The Journal of experimental medicine
Related Resources
PubMed ID
9841925
Repository Citation
Bukrinskaya AG, Brichacek B, Mann A, Stevenson M. (1998). Establishment of a functional human immunodeficiency virus type 1 (HIV-1) reverse transcription complex involves the cytoskeleton. Open Access Articles. Retrieved from https://escholarship.umassmed.edu/oapubs/1042