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Cell Rep. 2019 Jul 9;28(2):460-471.e5. doi: 10.1016/j.celrep.2019.06.022.

Evolution-Driven Attenuation of Alphaviruses Highlights Key Glycoprotein Determinants Regulating Viral Infectivity and Dissemination.

Author information

1
Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA.
2
Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA. Electronic address: kenneth.stapleford@nyumc.org.

Abstract

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.

KEYWORDS:

E1 glycoprotein; alphaviruses; chikungunya virus; cholesterol dependence; fusion; viral dissemination

PMID:
31291581
DOI:
10.1016/j.celrep.2019.06.022
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