Histone Deacetylase 2 Is a Component of Influenza A Virus-Induced Host Antiviral Response.

Host cells produce variety of antiviral factors that create an antiviral state and target various stages of influenza A virus (IAV) life cycle to inhibit infection. However, IAV has evolved various strategies to antagonize those antiviral factors. Recently, we reported that a member of class I host histone deacetylases (HDACs), HDAC1 possesses an anti-IAV function. Herein, we provide evidence that HDAC2, another class I member and closely related to HDAC1 in structure and function, also possesses anti-IAV properties. In turn, IAV, like HDAC1, dysregulates HDAC2, mainly at the polypeptide level through proteasomal degradation to potentially minimize its antiviral effect. We found that IAV downregulated the HDAC2 polypeptide level in A549 cells in an H1N1 strain-independent manner by up to 47%, which was recovered to almost 100% level in the presence of proteasome-inhibitor MG132. A further knockdown in HDAC2 expression by up to 90% via RNA interference augmented the growth kinetics of IAV in A549 cells by more than four-fold after 24 h of infection. Furthermore, the knockdown of HDAC2 expression decreased the IAV-induced phosphorylation of the transcription factor, Signal Transducer and Activator of Transcription I (STAT1) and the expression of interferon-stimulated gene, viperin in infected cells by 41 and 53%, respectively. The role of HDAC2 in viperin expression was analogous to that of HDAC1, but it was not in the phosphorylation of STAT1. This indicated that, like HDAC1, HDAC2 is a component of IAV-induced host innate antiviral response and performs both redundant and non-redundant functions vis-a-vis HDAC1; however, IAV dysregulates them both in a redundant manner.

Gold Nanoparticles Decorated with Sialic Acid Terminated Bi-antennary N-Glycans for the Detection of Influenza Virus at Nanomolar Concentrations.

Invited for this month's cover picture is the group of Professor Antony Fairbanks and his collaborators at the University of Canterbury and University of Otago. The cover shows the isolation of complex bi-antennary oligosaccharides from hens' eggs and their conjugation to gold nanoparticles. Gold nanoparticles carrying these sugars can then bind to specific receptors (hemagglutinin) on the surface of the influenza virus, causing particle aggregation, which changes their spectroscopic properties. Upon aggregation, they undergo a red-shift in their surface plasmon resonance, as illustrated by the bound particles shining in the cover image. These changes in spectroscopic properties are the basis of a detection system capable of detecting viral hemagglutinin at nanomolar concentrations, as well as the virus itself. For more details, see the Full Paper on p. 708 ff.Read the full text of the article at 10.1002/open.201500109.

Gold Nanoparticles Decorated with Sialic Acid Terminated Bi-antennary N-Glycans for the Detection of Influenza Virus at Nanomolar Concentrations.

Gold nanoparticles decorated with full-length sialic acid terminated complex bi-antennary N-glycans, synthesized with glycans isolated from egg yolk, were used as a sensor for the detection of both recombinant hemagglutinin (HA) and whole influenza A virus particles of the H1N1 subtype. Nanoparticle aggregation was induced by interaction between the sialic acid termini of the glycans attached to gold and the multivalent sialic acid binding sites of HA. Both dynamic light scattering (DLS) and UV/Vis spectroscopy demonstrated the efficiency of the sensor, which could detect viral HA at nanomolar concentrations and revealed a linear relationship between the extent of nanoparticle aggregation and the concentration of HA. UV/Vis studies also showed that these nanoparticles can selectively detect an influenza A virus strain that preferentially binds sialic acid terminated glycans with α(2→6) linkages over a strain that prefers glycans with terminal α(2→3)-linked sialic acids.