Evolution-Driven Attenuation of Alphaviruses Highlights Key Glycoprotein Determinants Regulating Viral Infectivity and Dissemination
Summary: 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...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-07-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719307880 |
| _version_ | 1811280215549149184 |
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| author | Maria G. Noval Bruno A. Rodriguez-Rodriguez Margarita V. Rangel Kenneth A. Stapleford |
| author_facet | Maria G. Noval Bruno A. Rodriguez-Rodriguez Margarita V. Rangel Kenneth A. Stapleford |
| author_sort | Maria G. Noval |
| collection | DOAJ |
| description | Summary: 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. : Noval et al. take an evolution-based approach to understand chikungunya virus (CHIKV) E1 glycoprotein function and highlight position 80 as a key determinant regulating CHIKV infectivity and spread in vivo, functioning through epistatic interactions with other glycoprotein residues to coordinate cholesterol-dependent entry. Keywords: alphaviruses, chikungunya virus, E1 glycoprotein, cholesterol dependence, fusion, viral dissemination |
| first_indexed | 2024-04-13T01:10:40Z |
| format | Article |
| id | doaj.art-0f62d92e71784384be3d9a94e29c87a0 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-13T01:10:40Z |
| publishDate | 2019-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-0f62d92e71784384be3d9a94e29c87a02022-12-22T03:09:10ZengElsevierCell Reports2211-12472019-07-01282460471.e5Evolution-Driven Attenuation of Alphaviruses Highlights Key Glycoprotein Determinants Regulating Viral Infectivity and DisseminationMaria G. Noval0Bruno A. Rodriguez-Rodriguez1Margarita V. Rangel2Kenneth A. Stapleford3Department of Microbiology, New York University School of Medicine, New York, NY 10016, USADepartment of Microbiology, New York University School of Medicine, New York, NY 10016, USADepartment of Microbiology, New York University School of Medicine, New York, NY 10016, USADepartment of Microbiology, New York University School of Medicine, New York, NY 10016, USA; Corresponding authorSummary: 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. : Noval et al. take an evolution-based approach to understand chikungunya virus (CHIKV) E1 glycoprotein function and highlight position 80 as a key determinant regulating CHIKV infectivity and spread in vivo, functioning through epistatic interactions with other glycoprotein residues to coordinate cholesterol-dependent entry. Keywords: alphaviruses, chikungunya virus, E1 glycoprotein, cholesterol dependence, fusion, viral disseminationhttp://www.sciencedirect.com/science/article/pii/S2211124719307880 |
| spellingShingle | Maria G. Noval Bruno A. Rodriguez-Rodriguez Margarita V. Rangel Kenneth A. Stapleford Evolution-Driven Attenuation of Alphaviruses Highlights Key Glycoprotein Determinants Regulating Viral Infectivity and Dissemination Cell Reports |
| title | Evolution-Driven Attenuation of Alphaviruses Highlights Key Glycoprotein Determinants Regulating Viral Infectivity and Dissemination |
| title_full | Evolution-Driven Attenuation of Alphaviruses Highlights Key Glycoprotein Determinants Regulating Viral Infectivity and Dissemination |
| title_fullStr | Evolution-Driven Attenuation of Alphaviruses Highlights Key Glycoprotein Determinants Regulating Viral Infectivity and Dissemination |
| title_full_unstemmed | Evolution-Driven Attenuation of Alphaviruses Highlights Key Glycoprotein Determinants Regulating Viral Infectivity and Dissemination |
| title_short | Evolution-Driven Attenuation of Alphaviruses Highlights Key Glycoprotein Determinants Regulating Viral Infectivity and Dissemination |
| title_sort | evolution driven attenuation of alphaviruses highlights key glycoprotein determinants regulating viral infectivity and dissemination |
| url | http://www.sciencedirect.com/science/article/pii/S2211124719307880 |
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