Rift Valley fever virus NSs inhibits host transcription independently of the degradation of dsRNA-dependent protein kinase PKR

Birte Kalveram, Olga Lihoradova, Sabarish V. Indran, Nandadeva Lokugamage, Jennifer A. Head, Tetsuro Ikegami

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Rift Valley fever virus (RVFV) encodes one major virulence factor, the NSs protein. NSs suppresses host general transcription, including interferon (IFN)-Β mRNA synthesis, and promotes degradation of the dsRNA-dependent protein kinase (PKR). We generated a novel RVFV mutant (rMP12-NSsR173A) specifically lacking the function to promote PKR degradation. rMP12-NSsR173A infection induces early phosphorylation of eIF2α through PKR activation, while retaining the function to inhibit host general transcription including IFN-Β gene inhibition. MP-12 NSs but not R173A NSs binds to wt PKR. R173A NSs formed filamentous structure in nucleus in a mosaic pattern, which was distinct from MP-12 NSs filament pattern. Due to early phosphorylation of eIF2α, rMP12-NSsR173A could not efficiently accumulate viral proteins. Our results suggest that NSs-mediated host general transcription suppression occurs independently of PKR degradation, while the PKR degradation is important to inhibit the phosphorylation of eIF2α in infected cells undergoing host general transcription suppression.

Original languageEnglish (US)
Pages (from-to)415-424
Number of pages10
JournalVirology
Volume435
Issue number2
DOIs
StatePublished - Jan 20 2013

Fingerprint

Rift Valley fever virus
eIF-2 Kinase
Phosphorylation
Interferons
Viral Proteins
Virulence Factors
Messenger RNA
Infection
Genes
Proteins
12-nitroxide stearate

Keywords

  • Bunyavirus
  • Interferon
  • MP-12
  • NSs protein
  • PKR
  • Reverse genetics
  • Rift Valley fever virus

ASJC Scopus subject areas

  • Virology

Cite this

Rift Valley fever virus NSs inhibits host transcription independently of the degradation of dsRNA-dependent protein kinase PKR. / Kalveram, Birte; Lihoradova, Olga; Indran, Sabarish V.; Lokugamage, Nandadeva; Head, Jennifer A.; Ikegami, Tetsuro.

In: Virology, Vol. 435, No. 2, 20.01.2013, p. 415-424.

Research output: Contribution to journalArticle

Kalveram, Birte ; Lihoradova, Olga ; Indran, Sabarish V. ; Lokugamage, Nandadeva ; Head, Jennifer A. ; Ikegami, Tetsuro. / Rift Valley fever virus NSs inhibits host transcription independently of the degradation of dsRNA-dependent protein kinase PKR. In: Virology. 2013 ; Vol. 435, No. 2. pp. 415-424.
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