AsianScientist (Sept. 4, 2017) – In a study published in the journal Proceedings of the National Academy of Sciences, scientists in China have reported the structure of the glycoprotein Gn from two viruses belonging to the bunyavirus family.
Bunyaviruses represent one of the largest RNA virus groups. Some members of the bunyavirus family, such as the Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) and the Rift Valley fever virus (RVFV), pose great threat to human health.
SFTSV and RVFV are the causative agents of febrile illnesses which can result in death from systemic organ failure. There are currently no vaccines or antiviral therapies against SFTSV and RVFV, and to date, little is known about the viruses’ target receptors, their mechanism of entry into cells and the organization of the two glycoproteins on their surfaces.
In this study, a team of researchers led by Professor Gao Fu and Dr. Gao Feng, both from the Chinese Academy of Sciences, determined the structure of the head domain of the glycoprotein Gn in SFTSV and RVFV. They found that for both viruses, the Gn head domain consist of three subdomains, and the overall fold of the Gn is similar in both viruses.
Interestingly, full-length Gn exists as monomers or dimers. Mass spectrometry analysis and mutation assay demonstrated that four cysteines located near the C-terminus of the glycoproteins are responsible for their dimerization.
Moreover, these cysteines are conserved among Hantaviridae, Nairoviridae, Tospoviridae, Phlebovirus in Phemuiviridae and Orthobunyavirus in Peribunyaviridae, thereby suggesting that the Gn dimer is probably the basic anchoring unit on the surface of these viruses.
The researchers also determined the structure of the SFTSV Gn head domain in complex with a neutralizing antibody, MAb 4-5. They showed that the helix structure, α6, in the Gn subdomain III is the key epitope recognized by MAb 4-5. Notably, this epitope is not conserved among bunyaviruses.
The binding mode illustrated by the Gn-antibody complex structure is expected to provide valuable information for the rational design of vaccines and antivirals against diseases caused by bunyaviruses.
The article can be found at: Wu et al. (2017) Structures of Phlebovirus Glycoprotein Gn and Identification of a Neutralizing Antibody Epitope.
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Source: Chinese Academy of Sciences; Photo: Gao et al.
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