The role of cell signaling in poxvirus tropism: The case of the M-T5 host range protein of myxoma virus

Steven J. Werden, Douglas McFadden

Research output: Contribution to journalReview article

33 Citations (Scopus)

Abstract

Poxviruses demonstrate strict species specificity in vivo that range from narrow to broad, however the fundamental factors that mediate the basis of poxvirus tropism remain poorly understood. It is generally believed that most, if not all, poxviruses can efficiently bind and enter a wide range of mammalian cells and all of the known host anti-viral pathways that block viral replication in nonpremissive cells operate downstream of virus entry. A productive poxvirus infection is heavily dependent upon the production of a vast array of host modulatory products that specifically target and manipulate both extracellular immune response pathways of the host, as well as intracellular signal transduction pathways of the individually infected cells. The unique pathogenesis and host tropism of specific poxviruses can be attributed to the broad diversity of host modulatory proteins they express. Myxoma virus (MV) is a rabbit-specific poxviruses that encodes multiple host range factors, including an ankyrin-repeat protein M-T5, which functions to regulate tropism of MV for rabbit lymphocytes and some human cancer cells. At the molecular level, M-T5 binds and alters at least two distinct cellular proteins: Akt and cullin-1. The direct interaction between M-T5 and Akt was shown to be a key restriction determinant for MV tropism in a spectrum of human cancer cells making MV an excellent oncolytic candidate. Thus, the intricate relationship between viral encoded proteins and components of the host cell signaling networks can have profound impact on poxvirus tropism. The lessons we continue to learn from poxvirus host range factors like M-T5 will provide further insights into the factors that regulate poxvirus tropism and the mechanisms by which poxviruses micromanipulate the signaling pathways of the infected cell.

Original languageEnglish (US)
Pages (from-to)228-237
Number of pages10
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Volume1784
Issue number1
DOIs
StatePublished - Jan 1 2008
Externally publishedYes

Fingerprint

Myxoma virus
Cell signaling
Poxviridae
Tropism
Host Specificity
Viruses
Cells
Proteins
Ankyrin Repeat
Signal transduction
Lymphocytes
Poxviridae Infections
Viral Tropism
Rabbits
Species Specificity
Virus Internalization
Viral Structures
Viral Proteins
Signal Transduction
Neoplasms

Keywords

  • Akt
  • Ankyrin repeat
  • F-box
  • Poxvirus
  • Protein kinase
  • Virus tropism

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

The role of cell signaling in poxvirus tropism : The case of the M-T5 host range protein of myxoma virus. / Werden, Steven J.; McFadden, Douglas.

In: Biochimica et Biophysica Acta - Proteins and Proteomics, Vol. 1784, No. 1, 01.01.2008, p. 228-237.

Research output: Contribution to journalReview article

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