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Cellular PSMB4 Protein Suppresses Influenza A Virus Replication through Targeting NS1 Protein
The nonstructural protein 1 (NS1) of influenza A virus (IAV) possesses multiple functions, such as the inhibition of the host antiviral immune responses, to facilitate viral infection. To search for cellular proteins interacting with the IAV NS1 protein, the yeast two-hybrid system was adopted. Prot...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9612107/ https://www.ncbi.nlm.nih.gov/pubmed/36298834 http://dx.doi.org/10.3390/v14102277 |
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author | Yang, Chee-Hing Hsu, Che-Fang Lai, Xiang-Qing Chan, Yu-Ru Li, Hui-Chun Lo, Shih-Yen |
author_facet | Yang, Chee-Hing Hsu, Che-Fang Lai, Xiang-Qing Chan, Yu-Ru Li, Hui-Chun Lo, Shih-Yen |
author_sort | Yang, Chee-Hing |
collection | PubMed |
description | The nonstructural protein 1 (NS1) of influenza A virus (IAV) possesses multiple functions, such as the inhibition of the host antiviral immune responses, to facilitate viral infection. To search for cellular proteins interacting with the IAV NS1 protein, the yeast two-hybrid system was adopted. Proteasome family member PSMB4 (proteasome subunit beta type 4) was found to interact with the NS1 protein in this screening experiment. The binding domains of these two proteins were also determined using this system. The physical interactions between the NS1 and cellular PSMB4 proteins were further confirmed by co-immunoprecipitation assay and confocal microscopy in mammalian cells. Neither transiently nor stably expressed NS1 protein affected the PSMB4 expression in cells. In contrast, PSMB4 reduced the NS1 protein expression level, especially in the presence of MG132. As expected, the functions of the NS1 protein, such as inhibition of interferon activity and enhancement of transient gene expression, were suppressed by PSMB4. PSMB4 knockdown enhances IAV replication, while its overexpression attenuates IAV replication. Thus, the results of this study suggest that the cellular PSMB4 protein interacts with and possibly facilitates the degradation of the NS1 protein, which in turn suppresses IAV replication. |
format | Online Article Text |
id | pubmed-9612107 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96121072022-10-28 Cellular PSMB4 Protein Suppresses Influenza A Virus Replication through Targeting NS1 Protein Yang, Chee-Hing Hsu, Che-Fang Lai, Xiang-Qing Chan, Yu-Ru Li, Hui-Chun Lo, Shih-Yen Viruses Article The nonstructural protein 1 (NS1) of influenza A virus (IAV) possesses multiple functions, such as the inhibition of the host antiviral immune responses, to facilitate viral infection. To search for cellular proteins interacting with the IAV NS1 protein, the yeast two-hybrid system was adopted. Proteasome family member PSMB4 (proteasome subunit beta type 4) was found to interact with the NS1 protein in this screening experiment. The binding domains of these two proteins were also determined using this system. The physical interactions between the NS1 and cellular PSMB4 proteins were further confirmed by co-immunoprecipitation assay and confocal microscopy in mammalian cells. Neither transiently nor stably expressed NS1 protein affected the PSMB4 expression in cells. In contrast, PSMB4 reduced the NS1 protein expression level, especially in the presence of MG132. As expected, the functions of the NS1 protein, such as inhibition of interferon activity and enhancement of transient gene expression, were suppressed by PSMB4. PSMB4 knockdown enhances IAV replication, while its overexpression attenuates IAV replication. Thus, the results of this study suggest that the cellular PSMB4 protein interacts with and possibly facilitates the degradation of the NS1 protein, which in turn suppresses IAV replication. MDPI 2022-10-17 /pmc/articles/PMC9612107/ /pubmed/36298834 http://dx.doi.org/10.3390/v14102277 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Yang, Chee-Hing Hsu, Che-Fang Lai, Xiang-Qing Chan, Yu-Ru Li, Hui-Chun Lo, Shih-Yen Cellular PSMB4 Protein Suppresses Influenza A Virus Replication through Targeting NS1 Protein |
title | Cellular PSMB4 Protein Suppresses Influenza A Virus Replication through Targeting NS1 Protein |
title_full | Cellular PSMB4 Protein Suppresses Influenza A Virus Replication through Targeting NS1 Protein |
title_fullStr | Cellular PSMB4 Protein Suppresses Influenza A Virus Replication through Targeting NS1 Protein |
title_full_unstemmed | Cellular PSMB4 Protein Suppresses Influenza A Virus Replication through Targeting NS1 Protein |
title_short | Cellular PSMB4 Protein Suppresses Influenza A Virus Replication through Targeting NS1 Protein |
title_sort | cellular psmb4 protein suppresses influenza a virus replication through targeting ns1 protein |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9612107/ https://www.ncbi.nlm.nih.gov/pubmed/36298834 http://dx.doi.org/10.3390/v14102277 |
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