Novel Viral Evasion Tactic Found from Influenza Virus H3N2

Abstract

Evaluation of: Marazzi I, Ho JSY, Kim J et al. Suppression of the antiviral response by an influenza histone mimic. Nature 483 (7390), 428–433 (2012). It is well known that to survive in cells, viruses have developed a variety of means to avoid host antiviral responses. Recently, Marazzi et al. reported a novel evasion tactic contributed by the NS1 of influenza virus H3N2. In contrast to other influenza subtypes such as H1N1 or H5N1, H3N2 contains a unique amino acid sequence of ARSK at the C-terminus of NS1, which is chemically similar to a functional domain ARTK at the N-terminus of histone H3 protein (histone tail) that has roles in regulating gene expression. This NS1 ARSK domain can mimic the histone tail to serve as a substrate for a variety of histone-modifying enzymes both in vitro and in vivo. The authors further showed that the NS1 histone mimic could bind directly to the human PAF1 transcription elongation complex (hPAF1C) to negatively regulate the ability of hPAF1C to drive the transcription of cellular antiviral genes. Disruption of hPAF1C and NS1 binding using mutagenesis either on the PAF1 subunit of hPAF1C or on NS1 resulted in reduction of virus replication. This novel evasion mechanism of NS1 to suppress the host antiviral response by acting as a histone mimic is interesting and has potential implications for the future development of novel antiviral strategies. However, this response appears to be limited to H3N2 virus, so the relevance to limiting future pandemics of other extremely pathogenic strains such as H1N1 or H5N1 remains to be determined.