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Caspase-Mediated Cleavage of Human Cortactin during Influenza A Virus Infection Occurs in Its Actin-Binding Domains and Is Associated with Released Virus Titres
Influenza A virus (IAV) exploits host factors to multiply and cause disease. An in-depth knowledge of this interaction of IAV with the host will aid the development of anti-IAV intervention strategies. Previously, we demonstrated that host cortactin, an actin filament-binding protein promotes IAV in...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019683/ https://www.ncbi.nlm.nih.gov/pubmed/31940955 http://dx.doi.org/10.3390/v12010087 |
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author | Chen, Da-Yuan Husain, Matloob |
author_facet | Chen, Da-Yuan Husain, Matloob |
author_sort | Chen, Da-Yuan |
collection | PubMed |
description | Influenza A virus (IAV) exploits host factors to multiply and cause disease. An in-depth knowledge of this interaction of IAV with the host will aid the development of anti-IAV intervention strategies. Previously, we demonstrated that host cortactin, an actin filament-binding protein promotes IAV infection, but undergoes degradation via a lysosome-associated apoptotic pathway during the late stages of IAV infection. Next, we wanted to further understand the mechanisms and significance of this phenomenon. By using the RNA interference screens and site-directed mutagenesis followed by western blotting, we found that lysosome protease, cathepsin C is involved in cortactin degradation in human cells infected with IAV. Furthermore, executioner apoptotic caspase, caspase-3 not caspase-6 or caspase-7 is involved in cortactin degradation during IAV infection, and caspase-3 cleavage site is located in the first actin-binding repeat of cortactin polypeptide. Finally, when expressed ectopically, the cleavage-resistant cortactin mutants decreased the amount of IAV progeny released from infected cells that was enhanced by the cleavage-sensitive cortactin wild type. These data strengthen the hypothesis proposed earlier that host cortactin plays an inhibitory role during the late stages of IAV infection, and IAV is facilitating its degradation to undermine such function. |
format | Online Article Text |
id | pubmed-7019683 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-70196832020-03-09 Caspase-Mediated Cleavage of Human Cortactin during Influenza A Virus Infection Occurs in Its Actin-Binding Domains and Is Associated with Released Virus Titres Chen, Da-Yuan Husain, Matloob Viruses Article Influenza A virus (IAV) exploits host factors to multiply and cause disease. An in-depth knowledge of this interaction of IAV with the host will aid the development of anti-IAV intervention strategies. Previously, we demonstrated that host cortactin, an actin filament-binding protein promotes IAV infection, but undergoes degradation via a lysosome-associated apoptotic pathway during the late stages of IAV infection. Next, we wanted to further understand the mechanisms and significance of this phenomenon. By using the RNA interference screens and site-directed mutagenesis followed by western blotting, we found that lysosome protease, cathepsin C is involved in cortactin degradation in human cells infected with IAV. Furthermore, executioner apoptotic caspase, caspase-3 not caspase-6 or caspase-7 is involved in cortactin degradation during IAV infection, and caspase-3 cleavage site is located in the first actin-binding repeat of cortactin polypeptide. Finally, when expressed ectopically, the cleavage-resistant cortactin mutants decreased the amount of IAV progeny released from infected cells that was enhanced by the cleavage-sensitive cortactin wild type. These data strengthen the hypothesis proposed earlier that host cortactin plays an inhibitory role during the late stages of IAV infection, and IAV is facilitating its degradation to undermine such function. MDPI 2020-01-12 /pmc/articles/PMC7019683/ /pubmed/31940955 http://dx.doi.org/10.3390/v12010087 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Chen, Da-Yuan Husain, Matloob Caspase-Mediated Cleavage of Human Cortactin during Influenza A Virus Infection Occurs in Its Actin-Binding Domains and Is Associated with Released Virus Titres |
title | Caspase-Mediated Cleavage of Human Cortactin during Influenza A Virus Infection Occurs in Its Actin-Binding Domains and Is Associated with Released Virus Titres |
title_full | Caspase-Mediated Cleavage of Human Cortactin during Influenza A Virus Infection Occurs in Its Actin-Binding Domains and Is Associated with Released Virus Titres |
title_fullStr | Caspase-Mediated Cleavage of Human Cortactin during Influenza A Virus Infection Occurs in Its Actin-Binding Domains and Is Associated with Released Virus Titres |
title_full_unstemmed | Caspase-Mediated Cleavage of Human Cortactin during Influenza A Virus Infection Occurs in Its Actin-Binding Domains and Is Associated with Released Virus Titres |
title_short | Caspase-Mediated Cleavage of Human Cortactin during Influenza A Virus Infection Occurs in Its Actin-Binding Domains and Is Associated with Released Virus Titres |
title_sort | caspase-mediated cleavage of human cortactin during influenza a virus infection occurs in its actin-binding domains and is associated with released virus titres |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019683/ https://www.ncbi.nlm.nih.gov/pubmed/31940955 http://dx.doi.org/10.3390/v12010087 |
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