Title

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

UMMS Affiliation

University of Massachusetts Medical School Program in Molecular Medicine

Publication Date

6-20-1998

Document Type

Article

Subjects

Antigens, CD4; Calcium-Calmodulin-Dependent Protein Kinases; Cell Line; Cell Membrane; Cell Nucleus; HIV Reverse Transcriptase; HIV-1; Hela Cells; Humans; Kidney; Kinetics; MAP Kinase Kinase 1; *Mitogen-Activated Protein Kinase Kinases; Polymerase Chain Reaction; Protein-Serine-Threonine Kinases; Protein-Tyrosine Kinases; Recombinant Fusion Proteins; Tetradecanoylphorbol Acetate; Transfection; Virion; Virus Replication

Disciplines

Life Sciences | Medicine and Health Sciences

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.

Rights and Permissions

Citation: EMBO J. 1998 May 1;17(9):2607-18. Link to article on publisher's site

DOI of Published Version

10.1093/emboj/17.9.2607

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

The EMBO journal

PubMed ID

9564043