Modulation of HIV-1 replication by a novel RhoA effector activity.
The RhoA GTPase is involved in regulating actin cytoskeletal organization, gene expression, cell proliferation, and survival. We report here that p115-RhoGEF, a specific guanine nucleotide exchange factor (GEF) and activator of RhoA, modulates HIV-1 replication. Ectopic expression of p115-RhoGEF or Galpha13, which activates p115-RhoGEF activity, leads to inhibition of HIV-1 replication. RhoA activation is required and the inhibition affects HIV-1 gene expression. The RhoA effector activity in inhibiting HIV-1 replication is genetically separable from its activities in transformation of NIH3T3 cells, activation of serum response factor, and actin stress fiber formation. These findings reveal that the RhoA signal transduction pathway regulates HIV-1 replication and suggest that RhoA inhibits HIV-1 replication via a novel effector activity.
Wang
L
L
Department of Microbiology, Lineberger Comprehensive Cancer Center, School of Medicine, School of Public Health, University of North Carolina, Chapel Hill, NC 27599, USA.
Zhang
H
H
Solski
P A
PA
Hart
M J
MJ
Der
C J
CJ
Su
L
L
D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000378:metabolism / Q000502:physiology; D002460:Cell Line; D005786:Gene Expression Regulation / Q000502:physiology; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism / Q000502:physiology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D064067:Rho Guanine Nucleotide Exchange Factors; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014779:Virus Replication / Q000235:genetics / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000502:physiology*
C576600:ARHGEF1 protein, human; D000998:Antiviral Agents; D020662:Guanine Nucleotide Exchange Factors; D064067:Rho Guanine Nucleotide Exchange Factors; D020742:rhoA GTP-Binding Protein