Infection of human cancer cells with myxoma virus requires Akt activation via interaction with a viral ankyrin-repeat host range factor

Gen Wang, John W. Barrett, Marianne Stanford, Steven J. Werden, James B. Johnston, Xiujuan Gao, Mei Sun, Jin Q. Cheng, Grant McFadden

Research output: Contribution to journalArticlepeer-review

130 Scopus citations

Abstract

We demonstrate that the susceptibility of human cancer cells to be infected and killed by an oncolytic poxvirus, myxoma virus (MV), is related to the basal level of endogenous phosphorylated Akt. We further demonstrate that nonpermissive tumor cells will switch from resistant to susceptible for MV infection after expression of ectopically active Akt (Myr-Akt) and that permissive cancer cells can be rendered nonpermissive by blocking Akt activation with a dominant-negative inhibitor of Akt. Finally, the activation of Akt by MV involves the formation of a complex between the viral host range ankyrin-repeat protein, M-T5, and Akt. We conclude that the Akt pathway is a key restriction determinant for permissiveness of human cancer cells by MV.

Original languageEnglish (US)
Pages (from-to)4640-4645
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number12
DOIs
StatePublished - Mar 21 2006
Externally publishedYes

Keywords

  • M-T5
  • Oncolytic virus
  • PkB
  • Poxvirus
  • Virus tropism

ASJC Scopus subject areas

  • General

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