Akt Inhibitor Akt-IV Blocks Virus Replication through an Akt-Independent Mechanism▿

AUTOR(ES)

Dunn, Ewan F.

FONTE

American Society for Microbiology (ASM)

RESUMO

Many viruses activate the phosphatidylinositol 3′-kinase (PI3k)/Akt intracellular signaling pathway to promote viral replication. We have analyzed whether a rapidly replicating rhabdovirus, vesicular stomatitis virus (VSV), requires the PI3k/Akt signaling pathway for its replication. Through the use of chemical inhibitors of PI3k and Akt, we show that VSV replication and cytopathic effects do not require activation of these kinases. Inhibitors that block the activating phosphorylations of Akt at threonine 308 (Thr308) and serine 473 (Ser473) did not inhibit VSV protein expression or the induction of the cytopathic effects of VSV. One compound, Akt inhibitor Akt-IV, inhibited the replication of VSV, respiratory syncytial virus, and vaccinia virus but increased the phosphorylation of Akt at positions Thr308 and Ser473 and did not inhibit Akt kinase activity in vitro. Together, our data suggest that the PI3k/Akt pathway is of limited relevance to the replication of VSV but that Akt inhibitor Akt-IV is a novel broad-spectrum antiviral compound with a mechanism differing from that of its previously reported effect on the PI3k/Akt pathway. Identification of other targets for this compound may define a new approach for blocking virus replication.

Documentos Relacionados

• AKT-Independent Protection of Prostate Cancer Cells from Apoptosis Mediated through Complex Formation between the Androgen Receptor and FKHR
• Sp1 Is Involved in Akt-mediated Induction of VEGF Expression through an HIF-1–independent Mechanism
• Cystatin C, a human proteinase inhibitor, blocks replication of herpes simplex virus.
• Protein Kinase B/Akt Regulates Coxsackievirus B3 Replication through a Mechanism Which Is Not Caspase Dependent
• p53-independent apoptosis induced by paclitaxel through an indirect mechanism