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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
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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. |
format | Online Article Text |
id | pubmed-7492085 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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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