Structure analysis of viral protein provides clues to how RVFV infects a cell

View:214 Time:2017-11-10

Viral infections are a serious threat to public health and livestock husbandry. Some viruses can be easily and efficiently transmitted to humans and/or animals by mosquitos. A recent study will help develop novel weapons to fight against these mosquito-borne viruses.

An international team of researchers has identified a mechanism by which Rift Valley fever virus (RVFV) infects a cell. The discovery would aid in the development of preventive and therapeutic strategies for Rift Valley fever (RVF), an acute, fever-causing disease that is most commonly observed in domesticated animals but also has the capacity to affect humans.

RVFV, a member of the Phlebovirus genus in the Bunyaviridae family, was first found in the 1930s during an epidemic in Kenya, Africa. Since then, outbreaks of RVFV have caused huge economic loss in Africa. Besides, the virus also causes mild to severe illness in humans. As the virus is spread by mosquitos, there is a potential risk of global spread. More effective vaccines and therapies are in need.

To elucidate how RVFV infects a host cell, researchers from Unité de Virologie Structurale, Institut Pasteur, Institut de Biologie Intégrative de la Cellule in France, University of Goettingen in Germany, and Utrecht University in Netherlands teamed up.

There are two important types of viral glycoproteins, Gn and Gc, on the surface of RVFV. The two glycoproteins are critical for attachment of the virus to a cell and its subsequent entry into the cell. In this work, the team obtained "the high-resolution crystal structure of RVFV class II fusion protein Gc in its postfusion form complexed with phosphatidylcholine." The detailed structural information allowed the researchers to find that the viral glycoprotein Gc has a specific pocket that recognizes certain components of cell membrane and drives target membrane insertion.

Notably, this recognition pocket is not only present in the fusion protein Gc of RVFV -- some other mosquito-borne viruses like Zika also have this recognition pocket. Therefore, the recognition pocket may be a target for antiviral therapies. Further, comparison of different viruses is a good method to study the mechanisms of viral infections, according to the researchers.

The study "A glycerophospholipid-specific pocket in the RVFV class II fusion protein drives target membrane insertion" appears 3 Nov 2017 in the journal Science.

RVFV can cause high mortality among young animals, bringing great economic damage. After entering the body via the bite of an infected mosquito, the virus can spread to various organs. For humans, the virus usually only cause mild symptoms that require no treatment, but it sometimes triggers severe disease, for which there is no specific treatment. There are no licensed vaccines for humans too. The live RVFV vaccines used for livestock have great disadvantages. The new study would improve prevention and treatment of RVFV infections.
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