A Zika virus envelope mutation preceding the 2015 epidemic enhances virulence and fitness for transmission

• DOI: 10.1073/pnas.2005722117
• Publication Date: 2020-08-04T00:26:28Z
• Authors: Chao Shan; Hongjie Xia; Sherry L. Haller; Sasha R. Azar; Yang Liu; Jianying Liu; Antonio E. Muruato; Rubing Chen; Shannan L. Rossi; Maki Wakamiya; Nikos Vasilakis; Rongjuan Pei; Camila R. Fontes-...; Sanjay Kumar Singh; Xuping Xie; Scott C. Weaver; Pei-Yong Shi
• Keywords: Viremia; Horizontal transmission; Zika Virus

Arboviruses maintain high mutation rates due to lack of proofreading ability their viral polymerases, in some cases facilitating adaptive evolution and emergence. Here we show that, just before its 2013 spread the Americas, Zika virus (ZIKV) underwent an envelope protein V473M substitution (E-V473M) that increased neurovirulence, maternal-to-fetal transmission, viremia facilitate urban transmission. A preepidemic Asian ZIKV strain (FSS13025 isolated Cambodia 2010) engineered with significantly neurovirulence neonatal mice produced higher loads placenta fetal heads pregnant mice. Conversely, epidemic (PRVABC59 Puerto Rico 2015) inverse M473V reversed pathogenic phenotypes. Although E-V473M did not affect oral infection Aedes aegypti mosquitoes, competition experiments cynomolgus macaques showed this fitness for generation, suggesting human hence Mechanistically, mutation, located at second transmembrane helix E protein, enhances virion morphogenesis. Overall, our study revealed as a critical determinant enhanced virulence, intrauterine transmission during pregnancy,