The chikungunya virus E1 glycoprotein fusion loop and hinge alter glycoprotein dynamics leading to cell and host specific changes in infectivity

• DOI: 10.1101/2023.11.03.565585
• Publication Date: 2023-11-05T21:30:17Z
• Authors: Sara A. Thannickal; Leandro Battini; Sophie N. Spector; Maria G. Noval; Diego E. Álvarez; Kenneth A. Staple...
• Keywords: Infectivity

Abstract Alphaviruses infect both mammals and insects, yet the distinct mechanisms that alphaviruses use to different hosts are not well defined. In this study, we characterize CHIKV E1 variants in fusion loop (E1-M88L) hinge region (E1-N20Y) vitro vivo understand how these regions of glycoprotein contribute host-specific infection. Through cell culture assays, found E1-N20Y enhanced infectivity mosquito cells while E1-M88L variant virus binding BHK-21 C6/36 cells, led changes cholesterol-dependence cells. Given results residue is a defined Mxra8 interacting domain, hypothesized may be important for receptor usage. However, increased replication Mxra8-deficient mice compared WT CHIKV, it was attenuated mouse fibroblasts, suggesting E1-M88 function cell-type dependent manner alter entry. Finally, using molecular dynamics potential impact E1-E2 complex, other domain II lead E2 dynamics. Taken together, studies show key residues through facilitate cell- host-dependent Importance Arthropod-borne viruses (arboviruses) significant global public health threats, their continued emergence around world highlights need replicate at level. The alphavirus class glycoproteins critical entry mosquitoes mammals, proteins completely understood. Therefore, address gaps our knowledge, dissect domains . Here, dynamics, furthering knowledge insects.