Architecture and antigenicity of the Nipah virus attachment glycoprotein.
Architecture and antigenicity of the Nipah virus attachment glycoprotein.
复制标题
尼帕病毒附着糖蛋白的结构和抗原性。
DOI：
10.1126/science.abm5561
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Veesler,David
中科院分区：
文献类型：
--
作者：
Wang,Zhaoqian;Amaya,Moushimi;Addetia,Amin;Dang,HaV;Reggiano,Gabriella;Yan,Lianying;Hickey,AndrewC;DiMaio,Frank;Broder,ChristopherC;Veesler,David
Nipah virus (NiV) and Hendra virus (HeV) are highly pathogenic zoonotic henipaviruses (HNVs) responsible for recurrent outbreaks of encephalitis and respiratory illness. As the current COVID-19 pandemic is gradually waning, attention is now being refocused on the nature of the next viral pandemic might be and what preparedness measures could be taken. Among almost all these discussions, the NiV Bangladesh strain (NiV-B) has been at the forefront of such concern by the scientific community, including the WHO and the Coalition for Epidemic Preparedness Innovations (CEPI). As another bat-borne virus, NiV infections are associated with human case fatality rates ranging from 40-95% and NiV-B is associated with significant human-to-human transmission. Currently, HNV G protein is both a vaccine antigen of interest for humans and a major viral target of monoclonal antibody therapy. Still, since the emergence of HeV in 1994 and NiV in 1998, no licensed treatments or vaccines for human use are yet available, but an approved equine vaccine is in use in Australia based on a soluble version of the HeV attachment G glycoprotein. However, the lack of structural information for any HNV G besides the receptor-binding head domain limits our understanding of viral infection and of host immunity. In this study, we successfully captured a high resolution Cryo-EM structure of NiV G protein ectodomain, revealed the intertwined architecture of this key therapeutic target and defined additional neutralization epitopes along with the potent antigen site, which all together providing a new platform for understanding the immunogenicity of HNV attachment protein as well as why it is such an important viral target of the immune response. These new findings and structural information will aid the development of both monoclonal antibody-based treatments and vaccine development strategies against these important zoonotic viral threats.
