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Dual Functions of Rift Valley Fever Virus NSs Protein: Inhibition of Host mRNA Transcription and Post‐transcriptional Downregulation of Protein Kinase PKR
Author(s) -
Ikegami Tetsuro,
Narayanan Krishna,
Won Sungyong,
Kamitani Wataru,
Peters C.J.,
Makino Shinji
Publication year - 2009
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2009.05054.x
Subject(s) - protein kinase r , rift valley fever , virology , phlebovirus , biology , interferon , bunyaviridae , transcription (linguistics) , virus , rna , viral protein , viral replication , rna silencing , protein kinase a , kinase , rna interference , gene , mitogen activated protein kinase kinase , microbiology and biotechnology , genetics , linguistics , philosophy
Rift Valley fever virus (RVFV), which belongs to the genus Phlebovirus , family Bunyaviridae , is a negative‐stranded RNA virus carrying a single‐stranded, tripartite RNA genome. RVFV is an important zoonotic pathogen transmitted by mosquitoes and causes large outbreaks among ruminants and humans in Africa and the Arabian Peninsula. Human patients develop an acute febrile illness, followed by a fatal hemorrhagic fever, encephalitis, or ocular diseases. A viral nonstructural protein, NSs, is a major viral virulence factor. Past studies showed that NSs suppresses the transcription of host mRNAs, including interferon‐β mRNAs. Here we demonstrated that the NSs protein induced post‐transcriptional downregulation of dsRNA‐dependent protein kinase (PKR), to prevent phosphorylation of eIF2α and promoted viral translation in infected cells. These two biological activities of the NSs most probably have a synergistic effect in suppressing host innate immune functions and facilitate efficient viral replication in infected mammalian hosts.