Modulation of HIV-1 infectivity by MAPK, a virion-associated kinase.
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.
Jacqué
J M
JM
University of Massachusetts Medical School, Program in Molecular Medicine, Worcester, MA 01605, USA.
Mann
A
A
Enslen
H
H
Sharova
N
N
Brichacek
B
B
Davis
R J
RJ
Stevenson
M
M
D015704:CD4 Antigens / Q000096:biosynthesis / Q000502:physiology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D002467:Cell Nucleus / Q000502:physiology; D054303:HIV Reverse Transcriptase / Q000378:metabolism; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D007668:Kidney; D007700:Kinetics; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D014771:Virion / Q000472:pathogenicity / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology
D015704:CD4 Antigens; D011993:Recombinant Fusion Proteins; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases; D054303:HIV Reverse Transcriptase; D013755:Tetradecanoylphorbol Acetate