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CCHFV envelope protein Gc in complex with Gc8
Structural highlights
FunctionGP_CCHFI Glycoprotein C and glycoprotein N interact with each other and are present at the surface of the virion. They are able to attach the virion to host cell receptors. This attachment induces virion internalization predominantly through clathrin-dependent endocytosis. Also promotes fusion of viral membrane with host endosomal membrane after endocytosis of the virion (By similarity).[1] Publication Abstract from PubMedCrimean-Congo hemorrhagic fever virus (CCHFV) is a highly pathogenic tick-borne virus, prevalent in more than 30 countries worldwide. Human infection by this virus leads to severe illness, with an average case fatality of 40%. There is currently no approved vaccine or drug to treat the disease. Neutralizing antibodies are a promising approach to treat virus infectious diseases. This study generated 37 mouse-derived specific monoclonal antibodies against CCHFV Gc subunit. Neutralization assays using pseudotyped virus and authentic CCHFV identified Gc8, Gc13, and Gc35 as neutralizing antibodies. Among them, Gc13 had the highest neutralizing activity and binding affinity with CCHFV Gc. Consistently, Gc13, but not Gc8 or Gc35, showed in vivo protective efficacy (62.5% survival rate) against CCHFV infection in a lethal mouse infection model. Further characterization studies suggested that Gc8 and Gc13 may recognize a similar, linear epitope in domain II of CCHFV Gc, while Gc35 may recognize a different epitope in Gc. Cryo-electron microscopy of Gc-Fab complexes indicated that both Gc8 and Gc13 bind to the conserved fusion loop region and Gc13 had stronger interactions with sGc-trimers. This was supported by the ability of Gc13 to block CCHFV GP-mediated membrane fusion. Overall, this study provides new therapeutic strategies to treat CCHF and new insights into the interaction between antibodies with CCHFV Gc proteins. Neutralizing monoclonal antibodies against the Gc fusion loop region of Crimean-Congo hemorrhagic fever virus.,Li L, Chong T, Peng L, Liu Y, Rao G, Fu Y, Shu Y, Shen J, Xiao Q, Liu J, Li J, Deng F, Yan B, Hu Z, Cao S, Wang M PLoS Pathog. 2024 Feb 1;20(2):e1011948. doi: 10.1371/journal.ppat.1011948. , eCollection 2024 Feb. PMID:38300972[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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