Evidence for a novel gene associated with human influenza A viruses

Abstract

BackgroundInfluenza A virus genomes are comprised of 8 negative strand single-stranded RNA segments and are thought to encode 11 proteins, which are all translated from mRNAs complementary to the genomic strands. Although human, swine and avian influenza A viruses are very similar, cross-species infections are usually limited. However, antigenic differences are considerable and when viruses become established in a different host or if novel viruses are created by re-assortment devastating pandemics may arise.ResultsExamination of influenza A virus genomes from the early 20th Century revealed the association of a 167 codon ORF encoded by the genomic strand of segment 8 with human isolates. Close to the timing of the 1948 pseudopandemic, a mutation occurred that resulted in the extension of this ORF to 216 codons. Since 1948, this ORF has been almost totally maintained in human influenza A viruses suggesting a selectable biological function. The discovery of cytotoxic T cells responding to an epitope encoded by this ORF suggests that it is translated into protein. Evidence of several other non-traditionally translated polypeptides in influenza A virus support the translation of this genomic strand ORF. The gene product is predicted to have a signal sequence and two transmembrane domains.ConclusionWe hypothesize that the genomic strand of segment 8 of encodes a novel influenza A virus protein. The persistence and conservation of this genomic strand ORF for almost a century in human influenza A viruses provides strong evidence that it is translated into a polypeptide that enhances viral fitness in the human host. This has important consequences for the interpretation of experiments that utilize mutations in the NS1 and NEP genes of segment 8 and also for the consideration of events that may alter the spread and/or pathogenesis of swine and avian influenza A viruses in the human population.

NSP protein encoded in negative NS RNA strand of influenza A virus induces cellular immune response in infected animals

“…[4]. В настоящее время экспрессия гена NSP при репликации вируса ещё не установлена [6][7][8][9]. Пока не известно, каким образом и в клетках каких тканей может синтезироваться белок NSP вирусов гриппа A. Однако в процессе его синтеза в целостном организме может формироваться гуморальный и/или клеточный иммунный ответ на данный вирусный белок.…”

Cellular immune response in infected mice to NSP protein encoded by the negative strand NS RNA of influenza A virus

“…These results confirm that the vRNA of segment 8 of human influenza A virus has a messenger translation function that is in accordance with the concept of bipolar (ambisense) influenza A viral genome strategy. Currently, the significance of the detected gene and the possibility of NSP protein expression during virus replication have not yet been established [9][10][11][12]. The importance of the positivepolar gene in the influenza A virus has been proved by the fact that, since the beginning of the 20th century until the present time, this gene remains fully functional in the genome of human viral strains despite the pronounced drift variability of the viral genome [6].…”

Genetic analysis of HA gene of pandemic H1N1 2009 influenza viruses circulating in India

“…In comparison to vaccine strain A/California/07/2009 [ Table 2 Analysis of all the selected HA proteins with multiple software tools including SignalP v3.0, Phobius, SPOCTOPUS and Signal-BLAST [15] showed that the N terminal of the HA protein as having a signal peptide which consists of about 17 amino acids and the cleavage site present between positions 17 and 18. HA is cleaved into a signal peptide when mature proteins are produced.…”