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Histone Deacetylase 6 Knockout Mice Exhibit Higher Susceptibility to Influenza A Virus Infection

The host innate defence against influenza virus infection is an intricate system with a plethora of antiviral factors involved. We have identified host histone deacetylase 6 (HDAC6) as an anti-influenza virus factor in cultured cells. Consistent with this, we report herein that HDAC6 knockout (KO) m...

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Autores principales: Zanin, Mark, DeBeauchamp, Jennifer, Vangala, Gowthami, Webby, Richard J., Husain, Matloob
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411611/
https://www.ncbi.nlm.nih.gov/pubmed/32640546
http://dx.doi.org/10.3390/v12070728
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author Zanin, Mark
DeBeauchamp, Jennifer
Vangala, Gowthami
Webby, Richard J.
Husain, Matloob
author_facet Zanin, Mark
DeBeauchamp, Jennifer
Vangala, Gowthami
Webby, Richard J.
Husain, Matloob
author_sort Zanin, Mark
collection PubMed
description The host innate defence against influenza virus infection is an intricate system with a plethora of antiviral factors involved. We have identified host histone deacetylase 6 (HDAC6) as an anti-influenza virus factor in cultured cells. Consistent with this, we report herein that HDAC6 knockout (KO) mice are more susceptible to influenza virus A/PR/8/1934 (H1N1) infection than their wild type (WT) counterparts. The KO mice lost weight faster than the WT mice and, unlike WT mice, could not recover their original body weight. Consequently, more KO mice succumbed to infection, which corresponded with higher lung viral loads. Conversely, the expression of the critical innate antiviral response genes interferon alpha/beta, CD80, CXCL10 and IL15 was significantly downregulated in KO mouse lungs compared to WT mouse lungs. These data are consistent with the known function of HDAC6 of de-acetylating the retinoic acid inducible gene-I (RIG-I) and activating the host innate antiviral response cascade. Loss of HDAC6 thus leads to a blunted innate response and increased susceptibility of mice to influenza A virus infection.
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spelling pubmed-74116112020-08-17 Histone Deacetylase 6 Knockout Mice Exhibit Higher Susceptibility to Influenza A Virus Infection Zanin, Mark DeBeauchamp, Jennifer Vangala, Gowthami Webby, Richard J. Husain, Matloob Viruses Article The host innate defence against influenza virus infection is an intricate system with a plethora of antiviral factors involved. We have identified host histone deacetylase 6 (HDAC6) as an anti-influenza virus factor in cultured cells. Consistent with this, we report herein that HDAC6 knockout (KO) mice are more susceptible to influenza virus A/PR/8/1934 (H1N1) infection than their wild type (WT) counterparts. The KO mice lost weight faster than the WT mice and, unlike WT mice, could not recover their original body weight. Consequently, more KO mice succumbed to infection, which corresponded with higher lung viral loads. Conversely, the expression of the critical innate antiviral response genes interferon alpha/beta, CD80, CXCL10 and IL15 was significantly downregulated in KO mouse lungs compared to WT mouse lungs. These data are consistent with the known function of HDAC6 of de-acetylating the retinoic acid inducible gene-I (RIG-I) and activating the host innate antiviral response cascade. Loss of HDAC6 thus leads to a blunted innate response and increased susceptibility of mice to influenza A virus infection. MDPI 2020-07-06 /pmc/articles/PMC7411611/ /pubmed/32640546 http://dx.doi.org/10.3390/v12070728 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
Zanin, Mark
DeBeauchamp, Jennifer
Vangala, Gowthami
Webby, Richard J.
Husain, Matloob
Histone Deacetylase 6 Knockout Mice Exhibit Higher Susceptibility to Influenza A Virus Infection
title Histone Deacetylase 6 Knockout Mice Exhibit Higher Susceptibility to Influenza A Virus Infection
title_full Histone Deacetylase 6 Knockout Mice Exhibit Higher Susceptibility to Influenza A Virus Infection
title_fullStr Histone Deacetylase 6 Knockout Mice Exhibit Higher Susceptibility to Influenza A Virus Infection
title_full_unstemmed Histone Deacetylase 6 Knockout Mice Exhibit Higher Susceptibility to Influenza A Virus Infection
title_short Histone Deacetylase 6 Knockout Mice Exhibit Higher Susceptibility to Influenza A Virus Infection
title_sort histone deacetylase 6 knockout mice exhibit higher susceptibility to influenza a virus infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411611/
https://www.ncbi.nlm.nih.gov/pubmed/32640546
http://dx.doi.org/10.3390/v12070728
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