A single mutation in the envelope protein modulates flavivirus antigenicity, stability, and pathogenesis

Author summary Flaviviruses include emerging pathogens such as WNV, DENV, and ZIKV that threaten global health. Despite causing significant morbidity, effective vaccines or therapeutic agents to protect humans against many flaviviruses are lacking. Because of the importance of antibodies in flavivirus immunity and vaccine protection, much effort is focused on understanding the factors that modulate antibody recognition of flaviviruses. Virus breathing, which allows viruses to sample different conformations at equilibrium, has the potential to transiently expose otherwise inaccessible antibody epitopes. Here, we report the identification a single mutation in the envelope protein that alters the exposure of a poorly accessible epitope and the stability of both WNV and DENV through changes in the ensemble of structures sampled by the virus. For WNV, this change attenuated infection and pathogenesis in mice, suggesting that virus conformational dynamics have relevant consequences in vivo.See it on Scoop.it, via Viruses and Bioinformatics from Virology.uvic.ca
A single mutation in the envelope protein modulates flavivirus antigenicity, stability, and pathogenesis
Source: Viral Bioinformatics