Cargando…
Enhanced stability of M1 protein mediated by a phospho-resistant mutation promotes the replication of prevailing avian influenza virus in mammals
Avian influenza virus (AIV) can evolve multiple strategies to combat host antiviral defenses and establish efficient infectivity in mammals, including humans. H9N2 AIV and its reassortants (such as H5N6 and H7N9 viruses) pose an increasing threat to human health; however, the mechanisms involved in...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9258882/ https://www.ncbi.nlm.nih.gov/pubmed/35793327 http://dx.doi.org/10.1371/journal.ppat.1010645 |
_version_ | 1784741650710396928 |
---|---|
author | Wang, Chenxi Qu, Runkang Zong, Yanan Qin, Chao Liu, Litao Gao, Xiaoyi Sun, Honglei Sun, Yipeng Chang, Kin-Chow Zhang, Rui Liu, Jinhua Pu, Juan |
author_facet | Wang, Chenxi Qu, Runkang Zong, Yanan Qin, Chao Liu, Litao Gao, Xiaoyi Sun, Honglei Sun, Yipeng Chang, Kin-Chow Zhang, Rui Liu, Jinhua Pu, Juan |
author_sort | Wang, Chenxi |
collection | PubMed |
description | Avian influenza virus (AIV) can evolve multiple strategies to combat host antiviral defenses and establish efficient infectivity in mammals, including humans. H9N2 AIV and its reassortants (such as H5N6 and H7N9 viruses) pose an increasing threat to human health; however, the mechanisms involved in their increased virulence remain poorly understood. We previously reported that the M1 mutation T37A has become predominant among chicken H9N2 isolates in China. Here, we report that, since 2010, this mutation has also been found in the majority of human isolates of H9N2 AIV and its emerging reassortants. The T37A mutation of M1 protein enhances the replication of H9N2 AIVs in mice and in human cells. Interestingly, having A37 instead of T37 increases the M1 protein stability and resistance to proteasomal degradation. Moreover, T37 of the H9N2 M1 protein is phosphorylated by protein kinase G (PKG), and this phosphorylation induces the rapid degradation of M1 and reduces viral replication. Similar effects are also observed in the novel H5N6 virus. Additionally, ubiquitination at K187 contributes to M1-37T degradation and decreased replication of the virus harboring T37 in the M1 protein. The prevailing AIVs thereby evolve a phospho-resistant mutation in the M1 protein to avoid viral protein degradation by host factors, which is advantageous in terms of replication in mammalian hosts. |
format | Online Article Text |
id | pubmed-9258882 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-92588822022-07-07 Enhanced stability of M1 protein mediated by a phospho-resistant mutation promotes the replication of prevailing avian influenza virus in mammals Wang, Chenxi Qu, Runkang Zong, Yanan Qin, Chao Liu, Litao Gao, Xiaoyi Sun, Honglei Sun, Yipeng Chang, Kin-Chow Zhang, Rui Liu, Jinhua Pu, Juan PLoS Pathog Research Article Avian influenza virus (AIV) can evolve multiple strategies to combat host antiviral defenses and establish efficient infectivity in mammals, including humans. H9N2 AIV and its reassortants (such as H5N6 and H7N9 viruses) pose an increasing threat to human health; however, the mechanisms involved in their increased virulence remain poorly understood. We previously reported that the M1 mutation T37A has become predominant among chicken H9N2 isolates in China. Here, we report that, since 2010, this mutation has also been found in the majority of human isolates of H9N2 AIV and its emerging reassortants. The T37A mutation of M1 protein enhances the replication of H9N2 AIVs in mice and in human cells. Interestingly, having A37 instead of T37 increases the M1 protein stability and resistance to proteasomal degradation. Moreover, T37 of the H9N2 M1 protein is phosphorylated by protein kinase G (PKG), and this phosphorylation induces the rapid degradation of M1 and reduces viral replication. Similar effects are also observed in the novel H5N6 virus. Additionally, ubiquitination at K187 contributes to M1-37T degradation and decreased replication of the virus harboring T37 in the M1 protein. The prevailing AIVs thereby evolve a phospho-resistant mutation in the M1 protein to avoid viral protein degradation by host factors, which is advantageous in terms of replication in mammalian hosts. Public Library of Science 2022-07-06 /pmc/articles/PMC9258882/ /pubmed/35793327 http://dx.doi.org/10.1371/journal.ppat.1010645 Text en © 2022 Wang 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 Wang, Chenxi Qu, Runkang Zong, Yanan Qin, Chao Liu, Litao Gao, Xiaoyi Sun, Honglei Sun, Yipeng Chang, Kin-Chow Zhang, Rui Liu, Jinhua Pu, Juan Enhanced stability of M1 protein mediated by a phospho-resistant mutation promotes the replication of prevailing avian influenza virus in mammals |
title | Enhanced stability of M1 protein mediated by a phospho-resistant mutation promotes the replication of prevailing avian influenza virus in mammals |
title_full | Enhanced stability of M1 protein mediated by a phospho-resistant mutation promotes the replication of prevailing avian influenza virus in mammals |
title_fullStr | Enhanced stability of M1 protein mediated by a phospho-resistant mutation promotes the replication of prevailing avian influenza virus in mammals |
title_full_unstemmed | Enhanced stability of M1 protein mediated by a phospho-resistant mutation promotes the replication of prevailing avian influenza virus in mammals |
title_short | Enhanced stability of M1 protein mediated by a phospho-resistant mutation promotes the replication of prevailing avian influenza virus in mammals |
title_sort | enhanced stability of m1 protein mediated by a phospho-resistant mutation promotes the replication of prevailing avian influenza virus in mammals |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9258882/ https://www.ncbi.nlm.nih.gov/pubmed/35793327 http://dx.doi.org/10.1371/journal.ppat.1010645 |
work_keys_str_mv | AT wangchenxi enhancedstabilityofm1proteinmediatedbyaphosphoresistantmutationpromotesthereplicationofprevailingavianinfluenzavirusinmammals AT qurunkang enhancedstabilityofm1proteinmediatedbyaphosphoresistantmutationpromotesthereplicationofprevailingavianinfluenzavirusinmammals AT zongyanan enhancedstabilityofm1proteinmediatedbyaphosphoresistantmutationpromotesthereplicationofprevailingavianinfluenzavirusinmammals AT qinchao enhancedstabilityofm1proteinmediatedbyaphosphoresistantmutationpromotesthereplicationofprevailingavianinfluenzavirusinmammals AT liulitao enhancedstabilityofm1proteinmediatedbyaphosphoresistantmutationpromotesthereplicationofprevailingavianinfluenzavirusinmammals AT gaoxiaoyi enhancedstabilityofm1proteinmediatedbyaphosphoresistantmutationpromotesthereplicationofprevailingavianinfluenzavirusinmammals AT sunhonglei enhancedstabilityofm1proteinmediatedbyaphosphoresistantmutationpromotesthereplicationofprevailingavianinfluenzavirusinmammals AT sunyipeng enhancedstabilityofm1proteinmediatedbyaphosphoresistantmutationpromotesthereplicationofprevailingavianinfluenzavirusinmammals AT changkinchow enhancedstabilityofm1proteinmediatedbyaphosphoresistantmutationpromotesthereplicationofprevailingavianinfluenzavirusinmammals AT zhangrui enhancedstabilityofm1proteinmediatedbyaphosphoresistantmutationpromotesthereplicationofprevailingavianinfluenzavirusinmammals AT liujinhua enhancedstabilityofm1proteinmediatedbyaphosphoresistantmutationpromotesthereplicationofprevailingavianinfluenzavirusinmammals AT pujuan enhancedstabilityofm1proteinmediatedbyaphosphoresistantmutationpromotesthereplicationofprevailingavianinfluenzavirusinmammals |