NSs protein of rift valley fever virus promotes posttranslational downregulation of the TFIIH subunit p62

Birte Kalveram, Olga Lihoradova, Tetsuro Ikegami

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus) is an important emerging pathogen of humans and ruminants. Its NSs protein has previously been identified as a major virulence factor that suppresses host defense through three distinct mechanisms: it directly inhibits beta interferon (IFN-β) promoter activity, it promotes the degradation of double-stranded RNA-dependent protein kinase (PKR), and it suppresses host transcription by disrupting the assembly of the basal transcription factor TFIIH through sequestration of its p44 subunit. Here, we report that in addition to PKR, NSs also promotes the degradation of the TFIIH subunit p62. Infection of cells with the RVFV MP-12 vaccine strain reduced p62 protein levels to below the detection limit early in the course of infection. This NSs-mediated downregulation of p62 was posttranslational, as it was unaffected by pharmacological inhibition of transcription or translation and MP-12 infection had no effect on p62 mRNA levels. Treatment of cells with proteasome inhibitors but not inhibition of lysosomal acidification or nuclear export resulted in a stabilization of p62 in the presence of NSs. Furthermore, p62 could be coprecipitated with NSs from lysates of infected cells. These data suggest that the RVFV NSs protein is able to interact with the TFIIH subunit p62 inside infected cells and promotes its degradation, which can occur directly in the nucleus.

Original languageEnglish (US)
Pages (from-to)6234-6243
Number of pages10
JournalJournal of Virology
Volume85
Issue number13
DOIs
StatePublished - Jul 2011

Fingerprint

Rift Valley fever virus
Down-Regulation
eIF-2 Kinase
degradation
Phlebovirus
Transcription Factor TFIIH
Proteins
proteins
transcription (genetics)
Infection
Bunyaviridae
infection
cells
interferon-beta
Proteasome Inhibitors
Cell Nucleus Active Transport
Double-Stranded RNA
Interferon-beta
double-stranded RNA
proteasome endopeptidase complex

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

NSs protein of rift valley fever virus promotes posttranslational downregulation of the TFIIH subunit p62. / Kalveram, Birte; Lihoradova, Olga; Ikegami, Tetsuro.

In: Journal of Virology, Vol. 85, No. 13, 07.2011, p. 6234-6243.

Research output: Contribution to journalArticle

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