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Open AccessArticle

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

1
State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, 195 Dongfengxi Rd, Guangzhou 510182, China
2
Department of Infectious Diseases, St Jude Children’s Research Hospital, Memphis, TN 38105, USA
3
Department of Microbiology and Immunology, University of Otago, Dunedin 9054, New Zealand
*
Author to whom correspondence should be addressed.
Viruses 2020, 12(7), 728; https://doi.org/10.3390/v12070728
Received: 2 June 2020 / Revised: 2 July 2020 / Accepted: 3 July 2020 / Published: 6 July 2020
(This article belongs to the Section Animal Viruses)
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. View Full-Text
Keywords: influenza A virus; IAV; histone deacetylase 6; HDAC6; knockout mice; type I interferon; CD80; CXCL10; IL15; RIG-I influenza A virus; IAV; histone deacetylase 6; HDAC6; knockout mice; type I interferon; CD80; CXCL10; IL15; RIG-I
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MDPI and ACS Style

Zanin, M.; DeBeauchamp, J.; Vangala, G.; Webby, R.J.; Husain, M. Histone Deacetylase 6 Knockout Mice Exhibit Higher Susceptibility to Influenza A Virus Infection. Viruses 2020, 12, 728.

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