Modified vaccinia virus Ankara can activate NF-kappaB transcription factors through a double-stranded RNA-activated protein kinase (PKR)-dependent pathway during the early phase of virus replication.

Published

Journal Article

Modified vaccinia virus Ankara (MVA), which is a promising replication-defective vaccine vector, is unusual among the orthopoxviruses in activating NF-kappaB transcription factors in cells of several types. In human embryonic kidney (HEK 293T) cells, the MVA-induced depletion of IkappaBalpha required to activate NF-kappaB is inhibited by UV-inactivation of the virus, and begins before viral DNA replication. In HEK 293T, CHO, or RK13 cells, expression of the cowpox virus CP77 early gene, or the vaccinia virus K1L early gene suppresses MVA-induced IkappaBalpha depletion. In mouse embryonic fibroblasts (MEFs), MVA induction of IkappaBalpha depletion is dependent on the expression of mouse or human double-stranded RNA-activated protein kinase (PKR). These results demonstrate that events during the early phase of MVA replication can induce PKR-mediated processes contributing both to the activation of NF-kappaB signaling, and to processes that may restrict viral replication. This property may contribute to the efficacy of this vaccine virus.

Full Text

Duke Authors

Cited Authors

  • Lynch, HE; Ray, CA; Oie, KL; Pollara, JJ; Petty, ITD; Sadler, AJ; Williams, BRG; Pickup, DJ

Published Date

  • September 2009

Published In

Volume / Issue

  • 391 / 2

Start / End Page

  • 177 - 186

PubMed ID

  • 19596385

Pubmed Central ID

  • 19596385

Electronic International Standard Serial Number (EISSN)

  • 1096-0341

International Standard Serial Number (ISSN)

  • 0042-6822

Digital Object Identifier (DOI)

  • 10.1016/j.virol.2009.06.012

Language

  • eng