title: The influenza A virus PB2, PA, NP, and M segments play a pivotal role during genome packaging.
abstract: The genomes of influenza A viruses consist of eight negative-strand RNA segments. Recent studies suggest that influenza viruses are able to specifically package their segmented genomes into the progeny virions. Segment-specific packaging signals of influenza virus RNAs (vRNAs) are located in the 5' and 3' noncoding regions, as well as in the terminal regions, of the open reading frames. How these packaging signals function during genome packaging remains unclear. Previously, we generated a 7-segmented virus in which the hemagglutinin (HA) and neuraminidase (NA) segments of the influenza A/Puerto Rico/8/34 virus were replaced by a chimeric influenza C virus hemagglutinin/esterase/fusion (HEF) segment carrying the HA packaging sequences. The robust growth of the HEF virus suggested that the NA segment is not required for the packaging of other segments. In this study, in order to determine the roles of the other seven segments during influenza A virus genome assembly, we continued to use this HEF virus as a tool and analyzed the effects of replacing the packaging sequences of other segments with those of the NA segment. Our results showed that deleting the packaging signals of the PB1, HA, or NS segment had no effect on the growth of the HEF virus, while growth was greatly impaired when the packaging sequence of the PB2, PA, nucleoprotein (NP), or matrix (M) segment was removed. These results indicate that the PB2, PA, NP, and M segments play a more important role than the remaining four vRNAs during the genome-packaging process.
authors.affiliation: Department of Microbiology, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: Qinshan
authors.initials: Q
authors.lastname: Gao
authors.forename: Yi-Ying
authors.initials: YY
authors.lastname: Chou
authors.forename: Sultan
authors.initials: S
authors.lastname: Doğanay
authors.forename: Reza
authors.initials: R
authors.lastname: Vafabakhsh
authors.forename: Taekjip
authors.initials: T
authors.lastname: Ha
authors.forename: Peter
authors.initials: P
authors.lastname: Palese
mesh_terms: D000818:Animals; D002460:Cell Line; D002642:Chick Embryo; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology*; D008969:Molecular Sequence Data; D019590:Nucleocapsid Proteins; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012324:RNA-Dependent RNA Polymerase / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D014758:Viral Core Proteins / Q000378:metabolism*; D014763:Viral Matrix Proteins / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*; D019065:Virus Assembly
chemical_list: C031540:M-protein, influenza virus; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; C061290:PA protein, influenza viruses; C502893:PB2 protein, influenza virus; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins; D014763:Viral Matrix Proteins; D014764:Viral Proteins; D012324:RNA-Dependent RNA Polymerase