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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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Autores principales: Chen, Da-Yuan, Husain, Matloob
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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.
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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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