M-T5, the ankyrin repeat, host range protein of myxoma virus, activates Akt and can be functionally replaced by cellular PIKE-A

Steven J. Werden, John W. Barrett, Gen Wang, Marianne M. Stanford, Douglas McFadden

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The myxoma virus (MV) ankyrin repeat, host range factor M-T5 has the ability to bind and activate cellular Akt, leading to permissive MV replication in a variety of diverse human cancer cell lines (G. Wang, J. W. Barrett, M. Stanford, S. J. Werden, J. B. Johnston, X. Gao, M. Sun, J. Q. Cheng, and G. McFadden, Proc. Natl. Acad. Sci. USA 103:4640-4645, 2006). The susceptibility of permissive human cancer cells to MV infection is directly correlated with the basal or induced levels of phosphorylated Akt. When M-T5 is deleted from MV, the knockout virus, vMyxT5KO, can no longer productively infect a subset of human cancer cells (designated type II) that exhibit little or no endogenous phosphorylated Akt. In searching for a host counterpart of M-T5, we noted sequence similarity of M-T5 to a recently identified ankyrin repeat cellular binding protein of Akt called PIKE-A. PIKE-A binds and activates the kinase activity of Akt in a GTP-dependent manner and promotes the invasiveness of human cancer cell lines. Here, we demonstrate that transfected PIKE-A is able to rescue the ability of vMyxT5KO to productively infect type II human cancer cells that were previously resistant to infection. Also, cancer cells that were completely nonpermissive for both wild-type and vMyxT5KO infection (called type III) were rendered fully permissive following ectopic expression of PIKE-A. We conclude that the MV M-T5 host range protein is functionally interchangeable with the host PIKE-A protein and that the activation of host Akt by either M-T5 or PIKE-A is critical for the permissiveness of human cancer cells for MV.

Original languageEnglish (US)
Pages (from-to)2340-2348
Number of pages9
JournalJournal of Virology
Volume81
Issue number5
DOIs
StatePublished - Mar 1 2007
Externally publishedYes

Fingerprint

Myxoma virus
Ankyrin Repeat
ankyrins
Host Specificity
host range
Neoplasms
Proteins
proteins
cell lines
Permissiveness
infection
Cell Line
host seeking
Aptitude
Virus Diseases
Virus Replication
virus replication
Guanosine Triphosphate
Infection
neoplasm cells

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

M-T5, the ankyrin repeat, host range protein of myxoma virus, activates Akt and can be functionally replaced by cellular PIKE-A. / Werden, Steven J.; Barrett, John W.; Wang, Gen; Stanford, Marianne M.; McFadden, Douglas.

In: Journal of Virology, Vol. 81, No. 5, 01.03.2007, p. 2340-2348.

Research output: Contribution to journalArticle

Werden, Steven J. ; Barrett, John W. ; Wang, Gen ; Stanford, Marianne M. ; McFadden, Douglas. / M-T5, the ankyrin repeat, host range protein of myxoma virus, activates Akt and can be functionally replaced by cellular PIKE-A. In: Journal of Virology. 2007 ; Vol. 81, No. 5. pp. 2340-2348.
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