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Mutational resilience of antiviral restriction favors primate TRIM5α in host-virus evolutionary arms races

Host antiviral proteins engage in evolutionary arms races with viruses, in which both sides rapidly evolve at interaction interfaces to gain or evade immune defense. For example, primate TRIM5α uses its rapidly evolving ‘v1’ loop to bind retroviral capsids, and single mutations in this loop can dram...

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Detalles Bibliográficos
Autores principales: Tenthorey, Jeannette L, Young, Candice, Sodeinde, Afeez, Emerman, Michael, Malik, Harmit S
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492085/
https://www.ncbi.nlm.nih.gov/pubmed/32930662
http://dx.doi.org/10.7554/eLife.59988
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author Tenthorey, Jeannette L
Young, Candice
Sodeinde, Afeez
Emerman, Michael
Malik, Harmit S
author_facet Tenthorey, Jeannette L
Young, Candice
Sodeinde, Afeez
Emerman, Michael
Malik, Harmit S
author_sort Tenthorey, Jeannette L
collection PubMed
description Host antiviral proteins engage in evolutionary arms races with viruses, in which both sides rapidly evolve at interaction interfaces to gain or evade immune defense. For example, primate TRIM5α uses its rapidly evolving ‘v1’ loop to bind retroviral capsids, and single mutations in this loop can dramatically improve retroviral restriction. However, it is unknown whether such gains of viral restriction are rare, or if they incur loss of pre-existing function against other viruses. Using deep mutational scanning, we comprehensively measured how single mutations in the TRIM5α v1 loop affect restriction of divergent retroviruses. Unexpectedly, we found that the majority of mutations increase weak antiviral function. Moreover, most random mutations do not disrupt potent viral restriction, even when it is newly acquired via a single adaptive substitution. Our results indicate that TRIM5α’s adaptive landscape is remarkably broad and mutationally resilient, maximizing its chances of success in evolutionary arms races with retroviruses.
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spelling pubmed-74920852020-09-16 Mutational resilience of antiviral restriction favors primate TRIM5α in host-virus evolutionary arms races Tenthorey, Jeannette L Young, Candice Sodeinde, Afeez Emerman, Michael Malik, Harmit S eLife Evolutionary Biology Host antiviral proteins engage in evolutionary arms races with viruses, in which both sides rapidly evolve at interaction interfaces to gain or evade immune defense. For example, primate TRIM5α uses its rapidly evolving ‘v1’ loop to bind retroviral capsids, and single mutations in this loop can dramatically improve retroviral restriction. However, it is unknown whether such gains of viral restriction are rare, or if they incur loss of pre-existing function against other viruses. Using deep mutational scanning, we comprehensively measured how single mutations in the TRIM5α v1 loop affect restriction of divergent retroviruses. Unexpectedly, we found that the majority of mutations increase weak antiviral function. Moreover, most random mutations do not disrupt potent viral restriction, even when it is newly acquired via a single adaptive substitution. Our results indicate that TRIM5α’s adaptive landscape is remarkably broad and mutationally resilient, maximizing its chances of success in evolutionary arms races with retroviruses. eLife Sciences Publications, Ltd 2020-09-15 /pmc/articles/PMC7492085/ /pubmed/32930662 http://dx.doi.org/10.7554/eLife.59988 Text en © 2020, Tenthorey et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Evolutionary Biology
Tenthorey, Jeannette L
Young, Candice
Sodeinde, Afeez
Emerman, Michael
Malik, Harmit S
Mutational resilience of antiviral restriction favors primate TRIM5α in host-virus evolutionary arms races
title Mutational resilience of antiviral restriction favors primate TRIM5α in host-virus evolutionary arms races
title_full Mutational resilience of antiviral restriction favors primate TRIM5α in host-virus evolutionary arms races
title_fullStr Mutational resilience of antiviral restriction favors primate TRIM5α in host-virus evolutionary arms races
title_full_unstemmed Mutational resilience of antiviral restriction favors primate TRIM5α in host-virus evolutionary arms races
title_short Mutational resilience of antiviral restriction favors primate TRIM5α in host-virus evolutionary arms races
title_sort mutational resilience of antiviral restriction favors primate trim5α in host-virus evolutionary arms races
topic Evolutionary Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492085/
https://www.ncbi.nlm.nih.gov/pubmed/32930662
http://dx.doi.org/10.7554/eLife.59988
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