Myxoma and vaccinia viruses exploit different mechanisms to enter and infect human cancer cells

Nancy Villa, Eric Bartee, Mohamed R. Mohamed, Masmudur Rahman, John W. Barrett, Douglas McFadden

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Myxoma (MYXV) and vaccinia (VACV) viruses have recently emerged as potential oncolytic agents that can infect and kill different human cancer cells. Although both are structurally similar, it is unknown whether the pathway(s) used by these poxviruses to enter and cause oncolysis in cancer cells are mechanistically similar. Here, we compared the entry of MYXV and VACV-WR into various human cancer cells and observed significant differences: 1 - low-pH treatment accelerates fusion-mediated entry of VACV but not MYXV, 2 - the tyrosine kinase inhibitor genistein inhibits entry of VACV, but not MYXV, 3 - knockdown of PAK1 revealed that it is required for a late stage event downstream of MYXV entry into cancer cells, whereas PAK1 is required for VACV entry into the same target cells. These results suggest that VACV and MYXV exploit different mechanisms to enter into human cancer cells, thus providing some rationale for their divergent cancer cell tropisms.

Original languageEnglish (US)
Pages (from-to)266-279
Number of pages14
JournalVirology
Volume401
Issue number2
DOIs
StatePublished - Jun 1 2010
Externally publishedYes

Fingerprint

Myxoma virus
Vaccinia virus
Neoplasms
TYK2 Kinase
Poxviridae
Myxoma
Tropism
Genistein

Keywords

  • Endocytosis
  • Entry-fusion complex
  • Genistein
  • Macropinocytosis
  • Myxoma
  • PAK1
  • Tyrosine kinase
  • Vaccinia

ASJC Scopus subject areas

  • Virology

Cite this

Myxoma and vaccinia viruses exploit different mechanisms to enter and infect human cancer cells. / Villa, Nancy; Bartee, Eric; Mohamed, Mohamed R.; Rahman, Masmudur; Barrett, John W.; McFadden, Douglas.

In: Virology, Vol. 401, No. 2, 01.06.2010, p. 266-279.

Research output: Contribution to journalArticle

Villa, Nancy ; Bartee, Eric ; Mohamed, Mohamed R. ; Rahman, Masmudur ; Barrett, John W. ; McFadden, Douglas. / Myxoma and vaccinia viruses exploit different mechanisms to enter and infect human cancer cells. In: Virology. 2010 ; Vol. 401, No. 2. pp. 266-279.
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