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

Zanin, Mark; DeBeauchamp, Jennifer; Vangala, Gowthami; Webby, Richard J.; Husain, Matloob

doi:10.3390/v12070728

Cited by 13 publications

(16 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To gain insight into the pro-viral mechanism of NAA60, we investigated its role in IAV-induced host innate antiviral response, because, previously, we identified that the HDACs exerts their anti-IAV function via this pathway ( 9 – 11 , 13 ). Furthermore, the IAV-induced expression of IFNα was downregulated in HDAC11-depleted cells ( 13 ) and HDAC6-knockout mice ( 14 ). To determine if the opposite was true in NAA60-depleted cells, A549 cells were transfected with the control or NAA60 siRNA and infected with PR8 at an MOI 1.0.…”

Section: Resultsmentioning

confidence: 99%

“…The acetyltransferases, Gcn5 and PCAF are involved in the suppression of the expression of host type I IFN and ISGs such as STAT1, MX1 and viperin ( 15 ), p300/CBP are implicated in the regulation, both positive and negative, of the expression of multiple host proteins involved in various stages of IAV life cycle ( 29 ), whereas NAA20/25 and also Gcn5 and PCAF facilitate the positive regulation of the IAV polymerase and host shutoff activities through acetylation of viral proteins ( 16 , 31 , 32 ). In contrast, HDAC6 ( 14 ) and HDAC11 ( 13 ) are involved in the enhancement of the IAV-induced type I IFN production. In addition, HDAC 1, 2, 4, and 11 also are implicated in the enhancement of the STAT1 phosphorylation as well as the expression of ISGs like viperin, IFITM3 and ISG15 during IAV infection ( 9 – 11 , 13 ).…”

Section: Discussionmentioning

confidence: 99%

“…Whereas the deacetylases are divided into four classes, of which class I, II, and IV are zinc-dependent histone or lysine deacetylases (HDACs or KDACs) and class III are NAD + -dependent sirtuins ( 6 ). We have discovered that acetylation promotes IAV infection ( 8 ) and at least one member of each class exhibits anti-IAV properties ( 9 – 14 ). Consistent with this, some HATs, e.g., GCN5 and PCAF ( 15 ), and NATs, NAA20 and NAA25 ( 16 ) have been shown to exhibit pro-IAV properties.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Human N-Alpha-Acetyltransferase 60 Promotes Influenza A Virus Infection by Dampening the Interferon Alpha Signaling

Ahmed

Husain

2022

Front. Immunol.

View full text Add to dashboard Cite

N-alpha-acetyltransferase 60 (NAA60) is the most recently discovered N-terminal acetyltransferase and found only in multicellular eukaryotes. NAA60 localizes to the Golgi complex and is one of the only two N-terminal acetyltransferases known to localize to an organelle. Furthermore, NAA60 possesses a unique ability of catalyzing the acetylation of membrane-anchored proteins at the N-terminus and histones at the lysine side chains. Herein, we demonstrate that NAA60 exhibits proviral properties during influenza A virus (IAV) infection by interfering with the interferon (IFN) α signaling. We found that the depletion and overexpression of NAA60 reduced and enhanced, respectively, the IAV growth in a cell type- and IAV strain-independent manner. Mechanistically, the IAV-induced expression of IFNα was increased and decreased in NAA60-depleted and -overexpressing cells, respectively. Furthermore, the depletion of NAA60 enhanced the level of phosphorylated STAT1 transcription factor as well as the expression of several IFN-stimulated genes (ISGs) such as MX1, CH25H, IFITM3, ISG15 and viperin in infected cells. Whereas the overexpression of NAA60 produced opposite results. Finally, similar results were obtained when the NAA60-depleted cells were treated with purified IFNα. These findings, in conjunction with our recent findings where N-terminal acetylation of many host proteins increased in response to the IAV infection, indicate an important role of N-terminal acetylation during IAV replication.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Human N-Alpha-Acetyltransferase 60 Promotes Influenza A Virus Infection by Dampening the Interferon Alpha Signaling

Ahmed

Husain

2022

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…This showed that the pro-viral role of HDAC6 ZnF domain during IAV uncoating influenced the infection outcome. In contrast, another recent study in which another strain of HDAC6 knockout mice was infected with IAV showed them to be more susceptible to PR8 H1N1 infection than their wild type counterpart [ 225 ]. In this work, it was argued that the absence of HDAC6 leads to a blunted innate response and concomitantly increased susceptibility of mice to IAV infection.…”

Section: In Focus: Influenza Virus Capsid Uncoatingmentioning

confidence: 99%

How Influenza Virus Uses Host Cell Pathways during Uncoating

Moreira

Yamauchi

Matthias

2021

Cells

View full text Add to dashboard Cite

Influenza is a zoonotic respiratory disease of major public health interest due to its pandemic potential, and a threat to animals and the human population. The influenza A virus genome consists of eight single-stranded RNA segments sequestered within a protein capsid and a lipid bilayer envelope. During host cell entry, cellular cues contribute to viral conformational changes that promote critical events such as fusion with late endosomes, capsid uncoating and viral genome release into the cytosol. In this focused review, we concisely describe the virus infection cycle and highlight the recent findings of host cell pathways and cytosolic proteins that assist influenza uncoating during host cell entry.

show abstract

“…Pharmacological inhibition of HDAC6 increased trafficking of viral components to the plasma membrane and viral release, a mechanism probably involving acetylated microtubules [ 313 ]. More recently, Hdac6 −/− mice were shown to be slightly more susceptible to influenza infection, which was actually correlated with a downregulation of several innate immune pathways [ 314 ]. Further clarification on the impact and the role of HDAC6 is therefore required.…”

Section: Iav Restriction Factorsmentioning

confidence: 99%

Mammalian and Avian Host Cell Influenza A Restriction Factors

McKellar

Rebendenne

Wencker

et al. 2021

Viruses

View full text Add to dashboard Cite

The threat of a new influenza pandemic is real. With past pandemics claiming millions of lives, finding new ways to combat this virus is essential. Host cells have developed a multi-modular system to detect incoming pathogens, a phenomenon called sensing. The signaling cascade triggered by sensing subsequently induces protection for themselves and their surrounding neighbors, termed interferon (IFN) response. This response induces the upregulation of hundreds of interferon-stimulated genes (ISGs), including antiviral effectors, establishing an antiviral state. As well as the antiviral proteins induced through the IFN system, cells also possess a so-called intrinsic immunity, constituted of antiviral proteins that are constitutively expressed, creating a first barrier preceding the induction of the interferon system. All these combined antiviral effectors inhibit the virus at various stages of the viral lifecycle, using a wide array of mechanisms. Here, we provide a review of mammalian and avian influenza A restriction factors, detailing their mechanism of action and in vivo relevance, when known. Understanding their mode of action might help pave the way for the development of new influenza treatments, which are absolutely required if we want to be prepared to face a new pandemic.

show abstract

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

Cited by 13 publications

References 29 publications

Human N-Alpha-Acetyltransferase 60 Promotes Influenza A Virus Infection by Dampening the Interferon Alpha Signaling

Human N-Alpha-Acetyltransferase 60 Promotes Influenza A Virus Infection by Dampening the Interferon Alpha Signaling

How Influenza Virus Uses Host Cell Pathways during Uncoating

Mammalian and Avian Host Cell Influenza A Restriction Factors

Contact Info

Product

Resources

About