Crystal structure of glycoprotein C from Rift Valley fever virus

Abstract

Rift Valley fever virus (RVFV), like many other Bunyaviridae family members, is an emerging human and animal pathogen. Bunyaviruses have an outer lipid envelope bearing two glycoproteins, G N and G C , required for cell entry. Bunyaviruses deliver their genome into the host-cell cytoplasm by fusing their envelope with an endosomal membrane. The molecular mechanism of this key entry step is unknown. The crystal structure of RVFV G C reveals a class II fusion protein architecture found previously in flaviviruses and alphaviruses. The structure identifies G C as the effector of membrane fusion and provides a direct view of the membrane anchor that initiates fusion. A structure of nonglycosylated G C reveals an extended conformation that may represent a fusion intermediate. Unanticipated similarities between G C and flavivirus envelope proteins reveal an evolutionary link between the two virus families and provide insights into the organization of G C in the outer shell of RVFV.

Structure of a phleboviral envelope glycoprotein reveals a consolidated model of membrane fusion

“…Similar to that observed for the Gc glycoprotein from the related RVFV Gc (17), SFTSV Gc eluted as a single monomeric species on size exclusion (SEC) at neutral pH (8.0). Upon acidification (5.0), we observed a mixture of monomeric and putative trimeric species, consistent with rearrangements of the molecule to a postfusion state ( Fig.…”

“…Interestingly, SFTSV is also capable of cell entry via extracellular vesicles, which likely allows evasion of the host immune system (16). Structural studies of the cognate Gc from RVFV (17) in the prefusion conformation revealed that the phleboviral Gc forms a class II architecture, which has been also observed for envelope glycoproteins from positive-sense RNA viruses from the Togaviridae and Flaviridae families (18,19). A similar class II architecture has also been observed in cell-cell fusion proteins, although the mechanism of membrane fusion is likely to differ from viral fusion as evident by the absence of a hydrophobic fusion loop (20).…”

Crystal structure of glycoprotein E2 from bovine viral diarrhea virus

“…Histidine side chains have pK a values in the range of 6-6.4 and therefore typically become protonated during endosomal acidification. The increase in positive charge resulting from histidine protonation is an important part of the pH sensing mechanism of many viruses (24)(25)(26)(27)(28)(29).…”

Nonmuscle Myosin Heavy Chain IIA Is a Critical Factor Contributing to the Efficiency of Early Infection of Severe Fever with Thrombocytopenia Syndrome Virus

“…Bunyavirus particles are enveloped with glycoproteins that form the spike-like surface responsible for attachment to host cells. Gn of Rift Valley fever virus forms a capsomer protruding from the virions and might retain receptor binding activity (7), while Gc of hantaviruses, Rift Valley fever virus, and other members of the Bunyaviridae family is believed to be a class II viral fusion protein responsible for viral fusion (8)(9)(10). Bunyaviruses invade host cells by interacting with cellular receptors (11); however, little is known about receptors and host factors for most bunyaviruses.…”