proteins

Structure of Rift Valley fever protein revealed

U. MICHIGAN (US)—Researchers have solved the structure of the nucleocapsid protein from Rift Valley fever virus (RVFV), so named for the region of sub-Saharan Africa where it was first isolated with outbreaks reported throughout the African continent as well as the Middle East.

RVFV infects livestock and humans and is most often transmitted by mosquitoes, usually after periods of heavy rain. The virus is also spread through the handling or consumption of infected meat. Effects of RVFV infection in humans are flu-like symptoms, encephalitis, hemorrhagic fever, and death.

The team’s findings were reported in PNAS.

The Rift Valley fever virus is a negative-sense RNA virus and part of a larger family of viruses called Bunyaviridae, which are characterized by an RNA genome that is completely covered, or “encapsidated”, by a viral protein known as N—the encapsidated viral RNA, known as a ribonucleoprotein (RNP), is essential for packaging the virus genome into a highly infectious particle.

University of Michigan research professor Janet Smith and colleagues used two powerful methods for seeing bio-molecules. They viewed the RNP with an electron microscope and solved the detailed atomic structure of the N protein using high-resolution X-ray crystallography.

The structures are the first from any virus in the Bunyaviridae family, and provided some unexpected results.

“The RNP structure was a surprise because researchers thought that all negative-sense viruses had encapsidated genomes with helical symmetry, like flu and other viruses studied previously” says Donald Raymond, coauthor of the paper. “Our crystal structure revealed that the N protein of bunyaviruses is different from N protein of other negative sense viruses and the electron microscope pictures of the ribonucleoprotein showed a lack of helical symmetry.”

The structures also revealed a conserved site on the N protein surface for critical contacts with other proteins. This is significant since protein-protein interactions that are crucial for the success of the virus are possible drug targets. Disrupting these interactions with drugs usually reduces the potency of the virus.

“Studying the structure of viral proteins provides insights into the overall architecture of the virus,” Raymond says. “Understanding how the virus is put together and how it uses the viral proteins may lead to drug targets and consequently the development of antiviral therapeutics.”

More University of Michigan news: www.ns.umich.edu/

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