The interaction between PRV gD and nectin-1.

Herpes virus membrane fusion requires the participation of multiple viral proteins and multiple cell surface receptors, coordination to complete, the whole process is extremely complex.
identification of the surface glycoprotein D(gD) and host cell receptor is an essential step in the early stages of alpha-herpes virus infection.
in the gD receptors that have been identified to date, the cell adhesion molecule nectin-1 is involved in the process of invading host cells of the alpha-herpes virus and is considered to be the most effective gD receptor.
therefore, the molecular mechanism of gD recognition of nectin-1 has become an important scientific issue in the field of alpha-herpes virus research.
The Gaofu team of the Institute of Microbiology of the Chinese Academy of Sciences and Yan Jinghua team have analyzed the complex structure of HSV gD and its receptamination nectin-1 in previous studies, and found that the HSV gD protein binds to the contact surface of nectin-1 molecular fusion.
this binding pattern destroys the integration of the nectin-1 itself, which in turn weakens cell adhesion and facilitates virus invasion (Nature Communications 2011; Journal of Virology 2014).
also shed light on the mechanism of interaction between gB, another key glycerin gB of the HSV virus, and the recepposor PILRa (PNAS 2014).
rabies virus (Pseudorabies virus, PRV) is the same as HSV alpha herpes virus.
HSV is a member of the Simplexvirus family, while PRV is a member of the Varicellovirus virus genus.
studies have shown that PRV can also use nectin-1 as a receptic, but its molecular mechanism is unclear.
addition, PRV infection host is a pig, then can it be combined with HSV receptors, such as human-sourced nectin-1, HVEM, etc., and thus there is a risk of human infection? The team systematically studied the interaction between PRV gD and nectin-1, proving that PRV can infect human-sourced and pig-sourced nectin-1 over-expressed cells, and that PRV gD has essentially the same affinity for nectin-1 from both sources, which serves as a warning against the risk of PRV infection in people.
study further analyzes the prV gD cell domain and its crystal structure with the nectin-1 complex. The
structure shows that the spatial structure of the PRV gD is very similar to that of the HSV, although its sequence is only 22% of the same, unlike the HSV gD structure, the LOOP area at the end of the PRV gD N-end is relatively short, and this area is exactly where the HSV gD binds to another recepcepor, which explains why the PRV cannot use HVEM as a recepcepor mechanism. The
composite structure indicates that PRV gD binds nectin-1 in the same pattern as HSV, however, there are several unique features in the PRV gD and nectin-1 binding interface that cause PRV binds to interact with nectin-1 using amino acid residues different from HSV gD.
The study not only reveals the molecular mechanisms of PRV gD's interaction with nectin-1, but also enriches the understanding of the receptament binding patterns of alpha-herpes virus subco, and also lays the theoretical foundation for the development of small molecular drugs that inhibit the fusion of pseudo-rabies virus.
the study was recently published in the journal PLOS Pathogens.
Li An, a Ph.D. student at the Institute of Microbiology of the Chinese Academy of Sciences and Guangxi University, and Yan Guangwen, a professor at Sichuan University, are the first co-authors, and Gao Fu, Yan Jinghua, and Luo Tingrong, a professor at Guangxi University, are co-authors of the paper.
research has been funded by national key research and development projects and a number of National Natural Science Foundation projects.
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