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Functional Insights into ANP32A-Dependent Influenza A Virus Polymerase Host Restriction
Host restriction of influenza A virus limits pandemic emergence. The viral RNA polymerase (vPol) is an essential enzyme that must adapt for avian viruses to replicate in humans. Species differences in host ANP32A dictate adaptation: human ANP32A lacks an uncharacterized 33 amino-acid insertion that...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5608968/ https://www.ncbi.nlm.nih.gov/pubmed/28903035 http://dx.doi.org/10.1016/j.celrep.2017.08.061 |
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author | Domingues, Patricia Hale, Benjamin G. |
author_facet | Domingues, Patricia Hale, Benjamin G. |
author_sort | Domingues, Patricia |
collection | PubMed |
description | Host restriction of influenza A virus limits pandemic emergence. The viral RNA polymerase (vPol) is an essential enzyme that must adapt for avian viruses to replicate in humans. Species differences in host ANP32A dictate adaptation: human ANP32A lacks an uncharacterized 33 amino-acid insertion that is present in avian ANP32A. Here, we uncover important contributions of host SUMOylation to vPol activity, including avANP32A function. We also identify a hydrophobic SUMO interaction motif (SIM)-like sequence unique to avANP32A that critically supports avian-signature vPol. Unrelated SIM sequences partially recapitulate this function when introduced into huANP32A. By investigating ANP32A-vPol interactions, we find that huANP32A interacts weakly with both human- and avian-signature vPols, while the hydrophobic motif of avANP32A promotes stronger interactions. Furthermore, we identify a highly acidic stretch in avANP32A that constitutes a major site of vPol interaction. Our data suggest compensatory mechanisms underlying vPol adaptation to host ANP32A independent of species-specific interactions. |
format | Online Article Text |
id | pubmed-5608968 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-56089682017-09-29 Functional Insights into ANP32A-Dependent Influenza A Virus Polymerase Host Restriction Domingues, Patricia Hale, Benjamin G. Cell Rep Report Host restriction of influenza A virus limits pandemic emergence. The viral RNA polymerase (vPol) is an essential enzyme that must adapt for avian viruses to replicate in humans. Species differences in host ANP32A dictate adaptation: human ANP32A lacks an uncharacterized 33 amino-acid insertion that is present in avian ANP32A. Here, we uncover important contributions of host SUMOylation to vPol activity, including avANP32A function. We also identify a hydrophobic SUMO interaction motif (SIM)-like sequence unique to avANP32A that critically supports avian-signature vPol. Unrelated SIM sequences partially recapitulate this function when introduced into huANP32A. By investigating ANP32A-vPol interactions, we find that huANP32A interacts weakly with both human- and avian-signature vPols, while the hydrophobic motif of avANP32A promotes stronger interactions. Furthermore, we identify a highly acidic stretch in avANP32A that constitutes a major site of vPol interaction. Our data suggest compensatory mechanisms underlying vPol adaptation to host ANP32A independent of species-specific interactions. Cell Press 2017-09-12 /pmc/articles/PMC5608968/ /pubmed/28903035 http://dx.doi.org/10.1016/j.celrep.2017.08.061 Text en © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Report Domingues, Patricia Hale, Benjamin G. Functional Insights into ANP32A-Dependent Influenza A Virus Polymerase Host Restriction |
title | Functional Insights into ANP32A-Dependent Influenza A Virus Polymerase Host Restriction |
title_full | Functional Insights into ANP32A-Dependent Influenza A Virus Polymerase Host Restriction |
title_fullStr | Functional Insights into ANP32A-Dependent Influenza A Virus Polymerase Host Restriction |
title_full_unstemmed | Functional Insights into ANP32A-Dependent Influenza A Virus Polymerase Host Restriction |
title_short | Functional Insights into ANP32A-Dependent Influenza A Virus Polymerase Host Restriction |
title_sort | functional insights into anp32a-dependent influenza a virus polymerase host restriction |
topic | Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5608968/ https://www.ncbi.nlm.nih.gov/pubmed/28903035 http://dx.doi.org/10.1016/j.celrep.2017.08.061 |
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