tetano
Editor, Senior Moderator
J Biol Chem. 2019 Nov 22. pii: jbc.RA119.010650. doi: 10.1074/jbc.RA119.010650. [Epub ahead of print] [h=1]Influenza A virus-induced host caspase and viral PA-X antagonise the antiviral host factor, histone deacetylase 4.[/h]
Galvin HD[SUP]1[/SUP], Husain M[SUP]2[/SUP].
[h=3]Author information[/h] 1 University of Otago, New Zealand. 2 Microbiology and Immunology, University of Otago, New Zealand.
[h=3]Abstract[/h] Influenza A virus (IAV) effectively manipulates host machinery to replicate. There is a growing evidence that an optimal acetylation environment in the host cell is favourable to IAV proliferation and vice versa. The histone deacetylases (HDACs) - a family of 18 host enzymes classified into four classes, are central to negatively regulating the acetylation level, hence the HDACs would not be favourable to IAV. Indeed, by using the RNA interference and overexpression strategies, we found that human HDAC4 - a class II member, possesses anti-IAV properties and is a component of host innate antiviral response. We discovered that IAV multiplication was augmented in HDAC4-depleted cells and abated in HDAC4-supplemented cells. Likewise, the expression of IFITM3, ISG15, and viperin - some of the critical markers of host anti-IAV response was abated in HDAC4-depleted cells and augmented in HDAC4-supplemented cells. In turn, IAV strongly antagonises the HDAC4, by downregulating its expression both at mRNA level via viral RNA endonuclease PA-X and at polypeptide level by inducing its cleavage via host caspase 3 in infected cells. Such HDAC4 polypeptide cleavage resulted in a ~30 kDa fragment which is also observed in some heterologous systems and may have a significant role in IAV replication.
Published under license by The American Society for Biochemistry and Molecular Biology, Inc.
[h=4]KEYWORDS:[/h] IFITM3; ISG15; PA; PA-X; histone deacetylase 4 (HDAC4); host defense; host-pathogen interaction; influenza virus; innate immunity; signal transducers and activators of transcription 1 (STAT1); viperin
PMID: 31757810 DOI: 10.1074/jbc.RA119.010650
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Galvin HD[SUP]1[/SUP], Husain M[SUP]2[/SUP].
[h=3]Author information[/h] 1 University of Otago, New Zealand. 2 Microbiology and Immunology, University of Otago, New Zealand.
[h=3]Abstract[/h] Influenza A virus (IAV) effectively manipulates host machinery to replicate. There is a growing evidence that an optimal acetylation environment in the host cell is favourable to IAV proliferation and vice versa. The histone deacetylases (HDACs) - a family of 18 host enzymes classified into four classes, are central to negatively regulating the acetylation level, hence the HDACs would not be favourable to IAV. Indeed, by using the RNA interference and overexpression strategies, we found that human HDAC4 - a class II member, possesses anti-IAV properties and is a component of host innate antiviral response. We discovered that IAV multiplication was augmented in HDAC4-depleted cells and abated in HDAC4-supplemented cells. Likewise, the expression of IFITM3, ISG15, and viperin - some of the critical markers of host anti-IAV response was abated in HDAC4-depleted cells and augmented in HDAC4-supplemented cells. In turn, IAV strongly antagonises the HDAC4, by downregulating its expression both at mRNA level via viral RNA endonuclease PA-X and at polypeptide level by inducing its cleavage via host caspase 3 in infected cells. Such HDAC4 polypeptide cleavage resulted in a ~30 kDa fragment which is also observed in some heterologous systems and may have a significant role in IAV replication.
Published under license by The American Society for Biochemistry and Molecular Biology, Inc.
[h=4]KEYWORDS:[/h] IFITM3; ISG15; PA; PA-X; histone deacetylase 4 (HDAC4); host defense; host-pathogen interaction; influenza virus; innate immunity; signal transducers and activators of transcription 1 (STAT1); viperin
PMID: 31757810 DOI: 10.1074/jbc.RA119.010650
Free full text