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The class IV human deacetylase, HDAC11 exhibits anti-influenza A virus properties via its involvement in host innate antiviral response

tetano

Editor, Senior Moderator
Cell Microbiol. 2018 Dec 4:e12989. doi: 10.1111/cmi.12989. [Epub ahead of print]
[h=1]The class IV human deacetylase, HDAC11 exhibits anti-influenza A virus properties via its involvement in host innate antiviral response.[/h] Nutsford AN[SUP]1[/SUP], Galvin HD[SUP]1[/SUP], Ahmed F[SUP]1[/SUP], Husain M[SUP]1[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] Histone deacetylase 11 (HDAC11) is most recently discovered deacetylase. Here, we demonstrate that human HDAC11 exhibits anti-influenza A virus (IAV) properties. We found that knockdown of HDAC11 expression augments IAV growth kinetics in human lung epithelial cells A549 by up to 1 log. One of the ways HDAC11 exerts its anti-IAV function is by being a part of IAV-induced host antiviral response. We found that the kinetics of both IAV- and interferon-induced innate antiviral response is significantly delayed in HDAC11-depleted cells. Further, in the absence of HDAC11 expression, there was a significant decrease in the expression of interferon-stimulated genes - IFITM3, ISG15, and viperin - previously implicated in anti-IAV function. One of the ways IAV antagonises HDAC11 is by downregulating its expression in host cells. We found that there was up to 93% reduction in HDAC11 transcript levels in A549 cells in response to IAV infection. HDAC11 is the smallest HDAC with majority of its polypeptide assigned to catalytic domain. Evolutionarily, it seems to be the least evolved and most closely related to common ancestral HDAC gene(s). Furthermore, HDAC11 has also been described as a deacylase. Therefore, our findings present exciting prospects for further investigations into significance of HDAC11 in virus infections.


[h=4]KEYWORDS:[/h] HDAC11; IFITM3; ISG15; Influenza virus; STAT1; antiviral host factors; histone deacetylase 11; innate immune response; viperin

PMID: 30511515 DOI: 10.1111/cmi.12989
 
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