title: Evolution of H5 highly pathogenic avian influenza: sequence data indicate stepwise changes in the cleavage site.
abstract: The genetic composition of an H5 subtype hemagglutinin gene quasispecies, obtained from ostrich tissues that had been infected with H5 subtype influenza virus was analysed using a next generation sequencing approach. The first evidence for the reiterative copying of a poly (U) stretch in the connecting peptide region in the haemagglutinin cleavage site (HACS) by the viral RNA-dependent RNA polymerase (RdRp) is provided. Multiple non-consensus species of RNA were detected in the infected host, corresponding to likely intermediate sequences between the putative low pathogenic precursor nucleotide sequence of the H5 influenza strain and the highly pathogenic avian influenza virus gene sequence. In silico analysis of the identified RNA sequences predicted that the intermediary H5 sequence PQREKRGLF plays an important role in subsequent mutational events that relocate the HACS coding region from stable base-paired RNA regions to a single-stranded bulge, thereby priming the connecting peptide coding region for RdRp slippage.
authors.affiliation: Department of Production Animal Studies, Faculty of Veterinary Science, University of Pretoria, Private Bag X04, Onderstepoort, Pretoria, 0110, South Africa. celia.abolnik@up.ac.za.
authors.forename: Celia
authors.identifier: http://orcid.org/0000-0003-3044-465X
authors.initials: C
authors.lastname: Abolnik
mesh_terms: D000818:Animals; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics* / Q000302:isolation & purification; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics* / Q000302:isolation & purification; D005585:Influenza in Birds / Q000821:virology*; D007251:Influenza, Human / Q000821:virology; D011200:Poultry / Q000821:virology; D012367:RNA, Viral / Q000235:genetics; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics*
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D012367:RNA, Viral; C109963:hemagglutinin, avian influenza A virus; D012324:RNA-Dependent RNA Polymerase