期刊
CELL REPORTS
卷 28, 期 2, 页码 460-+出版社
CELL PRESS
DOI: 10.1016/j.celrep.2019.06.022
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资金
- Jan Vilcek/David Goldfarb Fellowship from the New York University Department of Microbiology, New York University
- Public Health Service Institutional Research Training Award [T32 AI007180]
Understanding the fundamental mechanisms of arbovirus transmission and pathogenesis is essential to develop strategies for treatment and prevention. We previously took an in vivo evolution-based approach and identified the chikungunya virus E1 glycoprotein residue 80 to play a critical role in viral transmission and pathogenesis. In this study, we address the genetic conservation and function of position 80 and demonstrate that this residue is a key determinant in alphavirus infectivity and dissemination through modulation of viral fusion and cholesterol dependence. In addition, in studying the evolution of position 80, we identified a network of glycoprotein residues, including epidemic determinants, that regulate virus dissemination and infectivity. These studies underscore the importance of taking evolution-based approaches to not only identify key viral determinants driving arbovirus transmission and pathogenesis but also to uncover fundamental aspects of arbovirus biology.
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