The Vaccinia Virus K1L Gene Product Inhibits Host NF-κB Activation by Preventing IκBα Degradation

Joanna L. Shisler, Xiao Lu Jin

Research output: Contribution to journalArticlepeer-review

Abstract

Vaccinia virus wild-type strains such as Ankara and WR synthesize proteins capable of inhibiting the activation of host NF-κB, a family of transcription factors that regulate the expression of inflammatory genes. In contrast, an infection by the attenuated MVA strain, whose genome lacks many immunoregulatory genes present in the DNA of its Ankara parent, induces NF-κB activation. Insertion of NF-κB inhibitory genes into the MVA DNA, then, would alter the MVA phenotype. By this method, a 5.2-kb region of Ankara DNA containing the K1L gene and two other genes that are absent in the MVA genome that was identified as NF-κB was inhibited in cells infected with the MVA/5.2kb virus. To determine if K1L was responsible, the relevant biological properties of both a recombinant MVA containing a copy of the WR strain's K1L (MVA/K1L) and a WR deletion mutant lacking the K1L gene (ΔK1L) were examined. Indeed, unlike its progenitor, the altered MVA halted degradation of the host regulatory protein IκBα-a key event in the pathway of transcriptional activation by NF-κB factors. Moreover, MVA/K1L gained the ability to repress artificially contrived and natural NF-κB-regulated expression of a transfected luciferase and the cellular tumor necrosis factor gene, respectively. In contrast, although these functions could also be performed by WR, the ΔK1L virus lost these abilities. Thus, one apparent molecular function of K1L is to prevent I⇆Bα degradation. This impediment to NF-κB-induced host proinflammatory gene expression, in turn, might enhance virus survival.

Original languageEnglish (US)
Pages (from-to)3553-3560
Number of pages8
JournalJournal of virology
Volume78
Issue number7
DOIs
StatePublished - Apr 2004

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Fingerprint

Dive into the research topics of 'The Vaccinia Virus K1L Gene Product Inhibits Host NF-κB Activation by Preventing IκBα Degradation'. Together they form a unique fingerprint.

Cite this