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

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.

SUBMITTER: Noval MG

PROVIDER: S-EPMC7141928 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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

Noval Maria G MG Rodriguez-Rodriguez Bruno A BA Rangel Margarita V MV Stapleford Kenneth A KA

Cell reports 20190701 2

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 diss ...[more]

PMID: 31291581

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Dataset Information

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

Publications

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

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