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 G alpha 13, which activates p115-RhoGEF activity, leads to inhibition of HI V-1 replication, RhoA activation is required and the inhibition affects HIV -1 gene expression. The RhoA effector activity in inhibiting HIV-1 replicat ion is genetically separable from its activities in transformation of NIH3T 3 cells, activation of serum response factor, and actin stress fiber format ion. These findings reveal that the RhoA signal transduction pathway regula tes HIV-1 replication and suggest that RhoA inhibits HIV-1 replication via a novel effector activity.