NSm protein of Rift Valley fever virus suppresses virus-induced apoptosis.

Abstract

Rift Valley fever virus (RVFV) is a member of the genus Phlebovirus within the family Bunyaviridae. It can cause severe epidemics among ruminants and fever, myalgia, a hemorrhagic syndrome, and/or encephalitis in humans. The RVFV M segment encodes the NSm and 78-kDa proteins and two major envelope proteins, Gn and Gc. The biological functions of the NSm and 78-kDa proteins are unknown; both proteins are dispensable for viral replication in cell cultures. To determine the biological functions of the NSm and 78-kDa proteins, we generated the mutant virus arMP-12-del21/384, carrying a large deletion in the pre-Gn region of the M segment. Neither NSm nor the 78-kDa protein was synthesized in arMP-12-del21/384-infected cells. Although arMP-12-del21/384 and its parental virus, arMP-12, showed similar growth kinetics and viral RNA and protein accumulation in infected cells, arMP-12-del21/384-infected cells induced extensive cell death and produced larger plaques than did arMP-12-infected cells. arMP-12-del21/384 replication triggered apoptosis, including the cleavage of caspase-3, the cleavage of its downstream substrate, poly(ADP-ribose) polymerase, and activation of the initiator caspases, caspase-8 and -9, earlier in infection than arMP-12. NSm expression in arMP-12-del21/384-infected cells suppressed the severity of caspase-3 activation. Further, NSm protein expression inhibited the staurosporine-induced activation of caspase-8 and -9, demonstrating that other viral proteins were dispensable for NSm's function in inhibiting apoptosis. RVFV NSm protein is the first identified Phlebovirus protein that has an antiapoptotic function.

• Authors: Sungyong Won, Tetsuro Ikegami, C J Peters, Shinji Makino
• Journal: Journal of virology (J Virol) Vol. 81 Issue 24 Pg. 13335-45 (Dec 2007) ISSN: 1098-5514 [Electronic] United States
• PMID: 17913816 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• RNA, Viral
• Viral Nonstructural Proteins
• Caspases

Topics

• Animals
• Apoptosis (drug effects)
• Caspases (metabolism)
• Cell Line
• Chlorocebus aethiops
• Enzyme Activation (drug effects)
• Humans
• Kidney (cytology, virology)
• Macrophages (virology)
• Mice
• RNA, Viral (analysis)
• Rift Valley fever virus (genetics, metabolism, pathogenicity, physiology)
• Vero Cells
• Viral Nonstructural Proteins (genetics, metabolism, pharmacology)
• Viral Plaque Assay
• Virus Replication