Abstract
Rift Valley fever virus (RVFV) is a bunyavirus endemic to Africa and the Arabian Peninsula that infects humans and livestock. The virus encodes two glycoproteins, Gn and Gc, which represent the major structural antigens and are responsible for host cell receptor binding and fusion. Both glycoproteins are organized on the virus surface as cylindrical hollow spikes that cluster into distinct capsomers with the overall assembly exhibiting an icosahedral symmetry. Currently, no experimental three-dimensional structure for any entire bunyavirus glycoprotein is available. Using fold recognition, we generated molecular models for both RVFV glycoproteins and found significant structural matches between the RVFV Gn protein and the influenza virus hemagglutinin protein and a separate match between RVFV Gc protein and Sindbis virus envelope protein E1. Using these models, the potential interaction and arrangement of both glycoproteins in the RVFV particle was analyzed, by modeling their placement within the cryo-electron microscopy density map of RVFV. We identified four possible arrangements of the glycoproteins in the virion envelope. Each assembly model proposes that the ectodomain of Gn forms the majority of the protruding capsomer and that Gc is involved in formation of the capsomer base. Furthermore, Gc is suggested to facilitate intercapsomer connections. The proposed arrangement of the two glycoproteins on the RVFV surface is similar to that described for the alphavirus E1-E2 proteins. Our models will provide guidance to better understand the assembly process of phleboviruses and such structural studies can also contribute to the design of targeted antivirals.
Highlights
Rift Valley fever virus (RVFV) is a member of the family Bunyaviridae, transmitted primarily by mosquitoes and is endemic throughout much of Africa and, in recent years in the Arabian Peninsula
Before obtaining fold recognition and molecular model predictions of the two RVFV glycoproteins, the primary amino acid sequences of the entire Gn and Gc were analyzed for predicted transmembrane domains (TMD), ecto- and endo-domains (CTD), glycosylation sites, and consensus secondary structure prediction elements (Figure 1A)
While many studies have focused on molecular aspects of transcription, replication, pathogenesis, and vaccine development, little is known about the structural organization and physical interactions of bunyavirus glycoproteins within the virion
Summary
Rift Valley fever virus (RVFV) is a member of the family Bunyaviridae (genus Phlebovirus), transmitted primarily by mosquitoes and is endemic throughout much of Africa and, in recent years in the Arabian Peninsula. The virus causes outbreaks in a wide range of vertebrate hosts, with humans and livestock being the most affected. Infection of livestock can result in economically disastrous abortion storms and high mortality among young animals. The virus causes a variety of pathologic effects with less than 1% of infections thought to result in fatal hemorrhagic fever or encephalitis (MMWR, 2007). During the outbreak in Kenya, from November 2006 to January 2007, the fatality rate in humans reached nearly 30% (MMWR, 2007). RVFV is considered a high consequence emerging infectious disease threat and is of concern as a bioterrorism agent.
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