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The E2 glycoprotein holds key residues for Mayaro virus adaptation to the urban Aedes aegypti mosquito

Adaptation to mosquito vectors suited for transmission in urban settings is a major driver in the emergence of arboviruses. To better anticipate future emergence events, it is crucial to assess their potential to adapt to new vector hosts. In this work, we used two different experimental evolution a...

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Autores principales: Cereghino, Chelsea, Roesch, Ferdinand, Carrau, Lucía, Hardy, Alexandra, Ribeiro-Filho, Helder V., Henrion-Lacritick, Annabelle, Koh, Cassandra, Marano, Jeffrey M., Bates, Tyler A., Rai, Pallavi, Chuong, Christina, Akter, Shamima, Vallet, Thomas, Blanc, Hervé, Elliott, Truitt J., Brown, Anne M., Michalak, Pawel, LeRoith, Tanya, Bloom, Jesse D., Marques, Rafael Elias, Saleh, Maria-Carla, Vignuzzi, Marco, Weger-Lucarelli, James
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10109513/
https://www.ncbi.nlm.nih.gov/pubmed/37018377
http://dx.doi.org/10.1371/journal.ppat.1010491
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author Cereghino, Chelsea
Roesch, Ferdinand
Carrau, Lucía
Hardy, Alexandra
Ribeiro-Filho, Helder V.
Henrion-Lacritick, Annabelle
Koh, Cassandra
Marano, Jeffrey M.
Bates, Tyler A.
Rai, Pallavi
Chuong, Christina
Akter, Shamima
Vallet, Thomas
Blanc, Hervé
Elliott, Truitt J.
Brown, Anne M.
Michalak, Pawel
LeRoith, Tanya
Bloom, Jesse D.
Marques, Rafael Elias
Saleh, Maria-Carla
Vignuzzi, Marco
Weger-Lucarelli, James
author_facet Cereghino, Chelsea
Roesch, Ferdinand
Carrau, Lucía
Hardy, Alexandra
Ribeiro-Filho, Helder V.
Henrion-Lacritick, Annabelle
Koh, Cassandra
Marano, Jeffrey M.
Bates, Tyler A.
Rai, Pallavi
Chuong, Christina
Akter, Shamima
Vallet, Thomas
Blanc, Hervé
Elliott, Truitt J.
Brown, Anne M.
Michalak, Pawel
LeRoith, Tanya
Bloom, Jesse D.
Marques, Rafael Elias
Saleh, Maria-Carla
Vignuzzi, Marco
Weger-Lucarelli, James
author_sort Cereghino, Chelsea
collection PubMed
description Adaptation to mosquito vectors suited for transmission in urban settings is a major driver in the emergence of arboviruses. To better anticipate future emergence events, it is crucial to assess their potential to adapt to new vector hosts. In this work, we used two different experimental evolution approaches to study the adaptation process of an emerging alphavirus, Mayaro virus (MAYV), to Ae. aegypti, an urban mosquito vector of many other arboviruses. We identified E2-T179N as a key mutation increasing MAYV replication in insect cells and enhancing transmission after escaping the midgut of live Ae. aegypti. In contrast, this mutation decreased viral replication and binding in human fibroblasts, a primary cellular target of MAYV in humans. We also showed that MAYV E2-T179N generates reduced viremia and displays less severe tissue pathology in vivo in a mouse model. We found evidence in mouse fibroblasts that MAYV E2-T179N is less dependent on the Mxra8 receptor for replication than WT MAYV. Similarly, exogenous expression of human apolipoprotein receptor 2 and Mxra8 enhanced WT MAYV replication compared to MAYV E2-T179N. When this mutation was introduced in the closely related chikungunya virus, which has caused major outbreaks globally in the past two decades, we observed increased replication in both human and insect cells, suggesting E2 position 179 is an important determinant of alphavirus host-adaptation, although in a virus-specific manner. Collectively, these results indicate that adaptation at the T179 residue in MAYV E2 may result in increased vector competence–but coming at the cost of optimal replication in humans–and may represent a first step towards a future emergence event.
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spelling pubmed-101095132023-04-18 The E2 glycoprotein holds key residues for Mayaro virus adaptation to the urban Aedes aegypti mosquito Cereghino, Chelsea Roesch, Ferdinand Carrau, Lucía Hardy, Alexandra Ribeiro-Filho, Helder V. Henrion-Lacritick, Annabelle Koh, Cassandra Marano, Jeffrey M. Bates, Tyler A. Rai, Pallavi Chuong, Christina Akter, Shamima Vallet, Thomas Blanc, Hervé Elliott, Truitt J. Brown, Anne M. Michalak, Pawel LeRoith, Tanya Bloom, Jesse D. Marques, Rafael Elias Saleh, Maria-Carla Vignuzzi, Marco Weger-Lucarelli, James PLoS Pathog Research Article Adaptation to mosquito vectors suited for transmission in urban settings is a major driver in the emergence of arboviruses. To better anticipate future emergence events, it is crucial to assess their potential to adapt to new vector hosts. In this work, we used two different experimental evolution approaches to study the adaptation process of an emerging alphavirus, Mayaro virus (MAYV), to Ae. aegypti, an urban mosquito vector of many other arboviruses. We identified E2-T179N as a key mutation increasing MAYV replication in insect cells and enhancing transmission after escaping the midgut of live Ae. aegypti. In contrast, this mutation decreased viral replication and binding in human fibroblasts, a primary cellular target of MAYV in humans. We also showed that MAYV E2-T179N generates reduced viremia and displays less severe tissue pathology in vivo in a mouse model. We found evidence in mouse fibroblasts that MAYV E2-T179N is less dependent on the Mxra8 receptor for replication than WT MAYV. Similarly, exogenous expression of human apolipoprotein receptor 2 and Mxra8 enhanced WT MAYV replication compared to MAYV E2-T179N. When this mutation was introduced in the closely related chikungunya virus, which has caused major outbreaks globally in the past two decades, we observed increased replication in both human and insect cells, suggesting E2 position 179 is an important determinant of alphavirus host-adaptation, although in a virus-specific manner. Collectively, these results indicate that adaptation at the T179 residue in MAYV E2 may result in increased vector competence–but coming at the cost of optimal replication in humans–and may represent a first step towards a future emergence event. Public Library of Science 2023-04-05 /pmc/articles/PMC10109513/ /pubmed/37018377 http://dx.doi.org/10.1371/journal.ppat.1010491 Text en © 2023 Cereghino et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Cereghino, Chelsea
Roesch, Ferdinand
Carrau, Lucía
Hardy, Alexandra
Ribeiro-Filho, Helder V.
Henrion-Lacritick, Annabelle
Koh, Cassandra
Marano, Jeffrey M.
Bates, Tyler A.
Rai, Pallavi
Chuong, Christina
Akter, Shamima
Vallet, Thomas
Blanc, Hervé
Elliott, Truitt J.
Brown, Anne M.
Michalak, Pawel
LeRoith, Tanya
Bloom, Jesse D.
Marques, Rafael Elias
Saleh, Maria-Carla
Vignuzzi, Marco
Weger-Lucarelli, James
The E2 glycoprotein holds key residues for Mayaro virus adaptation to the urban Aedes aegypti mosquito
title The E2 glycoprotein holds key residues for Mayaro virus adaptation to the urban Aedes aegypti mosquito
title_full The E2 glycoprotein holds key residues for Mayaro virus adaptation to the urban Aedes aegypti mosquito
title_fullStr The E2 glycoprotein holds key residues for Mayaro virus adaptation to the urban Aedes aegypti mosquito
title_full_unstemmed The E2 glycoprotein holds key residues for Mayaro virus adaptation to the urban Aedes aegypti mosquito
title_short The E2 glycoprotein holds key residues for Mayaro virus adaptation to the urban Aedes aegypti mosquito
title_sort e2 glycoprotein holds key residues for mayaro virus adaptation to the urban aedes aegypti mosquito
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10109513/
https://www.ncbi.nlm.nih.gov/pubmed/37018377
http://dx.doi.org/10.1371/journal.ppat.1010491
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