Influenza A virus-induced host caspase and viral PA-X antagonize the antiviral host factor, histone deacetylase 4

Galvin, Henry D.; Husain, Matloob

doi:10.1074/jbc.ra119.010650

Cited by 25 publications

(39 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The HDACs are a family of 18 members which are classified into four classes. We and others have found that at least one member of each class, including a class II member histone deacetylase 6 (HDAC6) [5,6] exhibits antiviral properties during IAV infection [7][8][9][10][11][12]. HDAC6 is a multi-substrate deacetylase with two catalytic domains [5,6] and has been shown to exert its anti-IAV function through multiple mechanisms.…”

Section: Introductionmentioning

confidence: 99%

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

Zanin

DeBeauchamp

Vangala

et al. 2020

Viruses

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

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

Zanin

DeBeauchamp

Vangala

et al. 2020

Viruses

Self Cite

View full text Add to dashboard Cite

show abstract

“…The strength of the PA-X shutoff activity varies between IAV strains but even in viruses with low PA-X shutoff activity (e.g., the lab-adapted WSN and PR8 strains), altering PA-X expression has phenotypic effects (Desmet et al 2013;Hussain et al 2018;Rigby et al 2019). Other postulated mechanisms include interactions with stress granules and histone deacetylase 4 (Khaperskyy et al 2012(Khaperskyy et al , 2014Galvin and Husain 2019). In sum, the picture is of a viral protein that limits cellular responses, including induction of innate immunity, to infection.…”

Section: Pa-xmentioning

confidence: 99%

Accessory Gene Products of Influenza A Virus

Pinto

Lycett

Gaunt

et al. 2020

Cold Spring Harb Perspect Med

View full text Add to dashboard Cite

“…The protein bands that were visualized by chemiluminescence or fluorescence and images were acquired on Odyssey Fc imaging system (LI-COR). Images were then exported as TIFF files, minimally adjusted for brightness and contrast, and composed in figures in Adobe Photoshop CC 2015 [7,15].…”

Section: Western Blottingmentioning

confidence: 99%

“…Quantitative real-time PCR was performed on ViiA 6 Real-Time PCR system (Applied Biosystems) using SYBR Green Select Master Mix (Life Technologies) and predesigned KiCqStart primers for mentioned caspases and cathepsins (Sigma-Aldrich). The primers for human beta-actin were 5 -GACGACATGGAGAAAATCTG-3 (Forward) and 5 -ATGATCTGGGTCATCTTCTC-3 (Reverse) [15].…”

Section: Quantitative Real-time Rt-pcrmentioning

confidence: 99%

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

Husain

2020

Viruses

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Influenza A virus-induced host caspase and viral PA-X antagonize the antiviral host factor, histone deacetylase 4

Cited by 25 publications

References 51 publications

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

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

Accessory Gene Products of Influenza A Virus

Caspase-Mediated Cleavage of Human Cortactin during Influenza A Virus Infection Occurs in Its Actin-Binding Domains and Is Associated with Released Virus Titres

Contact Info

Product

Resources

About