Poster Presentation 9th Australasian Virology Society Meeting 2017

The redundancy in anti-influenza viral mechanism and antagonism of host histone deacetylase ‘twins’ (#127)

Matloob Husain 1
  1. University of Otago, Dunedin, OTAGO, New Zealand

Host cells promptly initiate the innate response after encountering a virion that sees the activation and expression of a plethora of host factors that create an antiviral state. These factors target various stages of virus life cycle to inhibit the progress of infection. In turn, viruses have evolved their own strategies to antagonize the antiviral host factors and successfully multiply.

We have discovered that at least two members of class I host histone deacetylases (HDACs), HDAC 1 and 2 possess anti-influenza A virus (IAV) properties. In turn, IAV dysregulates them both to potentially minimize their antiviral effect. We found that IAV, in an H1N1 strain-independent manner, downregulated the HDAC 1 and 2 polypeptide levels in human lung epithelial cells by 67% and 47%, respectively, after 24h of infection. However, such downregulated levels of both HDAC 1 and 2 polypeptides were recovered to almost 100% in the presence of proteasome inhibitor, MG132. A further, up to 97% and 90%, knockdown in the expression of HDAC 1 and 2 via RNA interference augmented the IAV growth kinetics by more than 3- and 4-fold, respectively, after 24h of infection. It looks that both HDAC 1 and 2 exert their anti-IAV function via viperin, an interferon-stimulate gene known to inhibit IAV infection, because the expression of viperin was reduced to 42% and 47% in infected cells depleted with HDAC 1 and 2 expression, respectively.

The HDAC 1 and 2 are practically ‘twins’ as they are closely-related in structure and exhibit many redundant functions in cell. The data generated so far also indicate this, as both HDAC 1 and 2 were found to be part of the IAV-induced host antiviral response and IAV dysregulated them both in a redundant manner. Nevertheless, there may be some non-redundancy in the IAV-HDAC1/2 interplay; further investigations will reveal that.

  1. Nagesh PT, Hussain M, Galvin HD, Husain M (2017). Histone deacetylase 2 is a component of influenza A virus-induced host antiviral response. Frontiers in Microbiology 8: 1315.
  2. Nagesh PT, Husain M. (2016). Influenza A virus dysregulates host histone deacetylase 1 that inhibits viral infection in lung epithelial cells. Journal of Virology 90 (9): 4614-4625.