Functional Analysis of Rift Valley Fever Virus NSs Encoding a Partial Truncation

Jennifer A. Head, Birte Kalveram, Tetsuro Ikegami

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Rift Valley fever virus (RVFV), belongs to genus Phlebovirus of the family Bunyaviridae, causes high rates of abortion and fetal malformation in infected ruminants as well as causing neurological disorders, blindness, or lethal hemorrhagic fever in humans. RVFV is classified as a category A priority pathogen and a select agent in the U.S., and currently there are no therapeutics available for RVF patients. NSs protein, a major virulence factor of RVFV, inhibits host transcription including interferon (IFN)-β mRNA synthesis and promotes degradation of dsRNA-dependent protein kinase (PKR). NSs self-associates at the C-terminus 17 aa., while NSs at aa.210-230 binds to Sin3A-associated protein (SAP30) to inhibit the activation of IFN-β promoter. Thus, we hypothesize that NSs function(s) can be abolished by truncation of specific domains, and co-expression of nonfunctional NSs with intact NSs will result in the attenuation of NSs function by dominant-negative effect. Unexpectedly, we found that RVFV NSs truncated at aa. 6-30, 31-55, 56-80, 81-105, 106-130, 131-155, 156-180, 181-205, 206-230, 231-248 or 249-265 lack functions of IFN-β mRNA synthesis inhibition and degradation of PKR. Truncated NSs were less stable in infected cells, while nuclear localization was inhibited in NSs lacking either of aa.81-105, 106-130, 131-155, 156-180, 181-205, 206-230 or 231-248. Furthermore, none of truncated NSs had exhibited significant dominant-negative functions for NSs-mediated IFN-β suppression or PKR degradation upon co-expression in cells infected with RVFV. We also found that any of truncated NSs except for intact NSs does not interact with RVFV NSs even in the presence of intact C-terminus self-association domain. Our results suggest that conformational integrity of NSs is important for the stability, cellular localization and biological functions of RVFV NSs, and the co-expression of truncated NSs does not exhibit dominant-negative phenotype.

Original languageEnglish (US)
Article numbere45730
JournalPLoS One
Volume7
Issue number9
DOIs
StatePublished - Sep 19 2012

Fingerprint

Rift Valley fever virus
Functional analysis
Viruses
interferons
Interferons
Degradation
degradation
Phlebovirus
Bunyaviridae
eIF-2 Kinase
Messenger RNA
abortion (animals)
synthesis
nervous system diseases
Induced Abortion
blindness
double-stranded RNA
Ruminants
Virulence Factors
Pathogens

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Functional Analysis of Rift Valley Fever Virus NSs Encoding a Partial Truncation. / Head, Jennifer A.; Kalveram, Birte; Ikegami, Tetsuro.

In: PLoS One, Vol. 7, No. 9, e45730, 19.09.2012.

Research output: Contribution to journalArticle

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