6hjc

Publication Abstract from PubMed

The emergence of Old and New World arenaviruses from rodent reservoirs persistently threatens human health. The GP1 subunit of the envelope-displayed arenaviral glycoprotein spike complex, GPC, mediates host-cell recognition and is an important determinant of cross-species transmission. Previous structural analyses of Old World arenaviral GP1 glycoproteins, alone and in complex with a cognate GP2 subunit, have revealed that GP1 adopts two distinct conformational states, distinguished by differences in orientation of helical regions of the molecule. Here, through comparative study of the GP1 glycoprotein architectures of Old World Loei River virus and New World Whitewater Arroyo virus, we show that these rearrangements are restricted to Old World arenaviruses and are not solely induced by the pH change that is associated with virus endosomal trafficking. Our structure-based phylogenetic analysis of arenaviral GP1s provides a blueprint for understanding the discrete structural classes adopted by these therapeutically important targets.IMPORTANCE The genetically and geographically diverse group of viruses within the Arenaviridae family includes a number of zoonotic pathogens capable of causing fatal hemorrhagic fever. The multi-subunit GPC glycoprotein spike complex displayed on the arenavirus envelope is a key determinant of species tropism and the primary target of the host humoral immune response. Here, we show that the receptor-binding GP1 sub-component of the GPC spike from Old World but not New World arenaviruses adopts a distinct, pH-independent conformation in the absence of the cognate GP2. Our analysis provides a structure-based approach for understanding the discrete conformational classes sampled by these therapeutically important targets, informing strategies to develop arenaviral glycoprotein immunogens that resemble GPC, as presented on the mature virion surface.

Structure-based classification defines the discrete conformational classes adopted by the arenaviral GP1.,Pryce R, Ng WM, Zeltina A, Watanabe Y, El Omari K, Wagner A, Bowden TA J Virol. 2018 Oct 10. pii: JVI.01048-18. doi: 10.1128/JVI.01048-18. PMID:30305351^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.