8dc5
From Proteopedia
CCHFV GP38 Hoti/Kosovo
Structural highlights
FunctionA0A7T6Y557_9VIRU Binds to host cell surface receptor LDLR and mediates fusion between viral and cellular membranes. Attachment to receptor induces virion internalization predominantly through clathrin-dependent endocytosis. Class II fusion protein that promotes fusion of viral membrane with host endosomal membrane after endocytosis of the virion. Exposure of the glycoprotein spikes to potassium is necessary for the conformational change leading to fusion.[PIRNR:PIRNR003962] Plays a role in virion attachment to host receptor. This attachment induces virion internalization predominantly through clathrin-dependent endocytosis. Glycoprotein N probably locks the Gn-Gc complex in a prefusion state.[PIRNR:PIRNR003962] Publication Abstract from PubMedCrimean-Congo Hemorrhagic Fever Virus (CCHFV) causes a life-threatening disease with up to a 40% mortality rate. With no approved medical countermeasures, CCHFV is considered a public health priority agent. The non-neutralizing mouse monoclonal antibody (mAb) 13G8 targets CCHFV glycoprotein GP38 and protects mice from lethal CCHFV challenge when administered prophylactically or therapeutically. Here, we reveal the structures of GP38 bound with a human chimeric 13G8 mAb and a newly isolated CC5-17 mAb from a human survivor. These mAbs bind overlapping epitopes with a shifted angle. The broad-spectrum potential of c13G8 and CC5-17 and the practicality of using them against Aigai virus, a closely related nairovirus were examined. Binding studies demonstrate that the presence of non-conserved amino acids in Aigai virus corresponding region prevent CCHFV mAbs from binding Aigai virus GP38. This information, coupled with in vivo efficacy, paves the way for future mAb therapeutics effective against a wide swath of CCHFV strains. Structural characterization of protective non-neutralizing antibodies targeting Crimean-Congo hemorrhagic fever virus.,Durie IA, Tehrani ZR, Karaaslan E, Sorvillo TE, McGuire J, Golden JW, Welch SR, Kainulainen MH, Harmon JR, Mousa JJ, Gonzalez D, Enos S, Koksal I, Yilmaz G, Karakoc HN, Hamidi S, Albay C, Spengler JR, Spiropoulou CF, Garrison AR, Sajadi MM, Bergeron E, Pegan SD Nat Commun. 2022 Nov 26;13(1):7298. doi: 10.1038/s41467-022-34923-0. PMID:36435827[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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