Modulation of HIV-1 infectivity by MAPK, a virion-associated kinase

Jean Marc Jacqué, Angela Mann, Hervé Enslen, Natalia Sharova, Beda Brichacek, Roger J. Davis, Mario Stevenson

Research output: Contribution to journalArticle

145 Scopus citations

Abstract

Infection of a cell by human immunodeficiency virus type 1 (HIV-1) results in the formation of a reverse transcription complex in which viral nucleic acids are synthesized. Efficient disengagement of the reverse transcription complex from the cell membrane and subsequent nuclear translocation require phosphorylation of reverse transcription complex components by a virion-associated kinase. In this study, we identify the virion-associated kinase as mitogen-activated protein kinase (ERK/MAPK). Upon density gradient fractionation, MAPK, but not its activating kinase MEK, co-sedimented with viral particles. Expression of a constitutively active, but not kinase-inactive, MEK1 in virus producer cells was able to activate virion-associated MAPK in trans. Stimulation of virion-associated MAPK activity in trans by the mitogen phorbol myristate acetate (PMA) increased viral infectivity. Conversely, suppression of virion-associated MAPK by specific inhibitors of the MAPK cascade markedly impaired viral infectivity. These studies demonstrate regulation of an early step in HIV-1 infection by the host cell MAPK signal transduction pathway.

Original languageEnglish (US)
Pages (from-to)2607-2618
Number of pages12
JournalEMBO Journal
Volume17
Issue number9
DOIs
StatePublished - May 1 1998

Keywords

  • HIV infectivity
  • MAP kinase

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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    Jacqué, J. M., Mann, A., Enslen, H., Sharova, N., Brichacek, B., Davis, R. J., & Stevenson, M. (1998). Modulation of HIV-1 infectivity by MAPK, a virion-associated kinase. EMBO Journal, 17(9), 2607-2618. https://doi.org/10.1093/emboj/17.9.2607