Unique Bipolar Gene Architecture in the RNA Genome of Influenza A Virus

The genome of influenza A virus consists of eight single-stranded negative-polarity RNA segments. The eighth segment (NS) encodes the anti-interferon protein NS1 (27 kDa) and the nuclear export protein NEP (14 kDa) via the classic negative-sense strategy. It also contains an additional positive-sense open reading frame that can be directly translated into the negative strand protein 8 (NSP8; 18–25 kDa in different strains). The existence of three or more genes of the opposite polarity in the same locus of a single-stranded RNA appears to be a unique (“economical”) type of gene architecture in living organisms. In silico analysis of genomes of human and animal influenza A viruses revealed that the NSP8 gene had emerged in the influenza A virus population about 100 years ago (“young” gene) and is highly evolutionary variable. The obtained experimental data suggest that NSP8 gene is expressed in the infected animals, which strengthens the concept of bipolar (ambisense) strategy of the influenza A virus genome. The high variability of the NSP8 protein suggests that the “young” NSP8 gene is in the process of functional optimization. Further accumulation of mutations may alter the functions of mature NSP8 protein and lead to the emergence of mature bipolar influenza A virus with unexpected properties that would be threatening for humans and animals.