title: Sequence analysis of in vivo defective interfering-like RNA of influenza A H1N1 pandemic virus.
abstract: Influenza virus defective interfering (DI) particles are naturally occurring noninfectious virions typically generated during in vitro serial passages in cell culture of the virus at a high multiplicity of infection. DI particles are recognized for the role they play in inhibiting viral replication and for the impact they have on the production of infectious virions. To date, influenza virus DI particles have been reported primarily as a phenomenon of cell culture and in experimentally infected embryonated chicken eggs. They have also been isolated from a respiratory infection of chickens. Using a sequencing approach, we characterize several subgenomic viral RNAs from human nasopharyngeal specimens infected with the influenza A(H1N1)pdm09 virus. The distribution of these in vivo-derived DI-like RNAs was similar to that of in vitro DIs, with the majority of the defective RNAs generated from the PB2 (segment 1) of the polymerase complex, followed by PB1 and PA. The lengths of the in vivo-derived DI-like segments also are similar to those of known in vitro DIs, and the in vivo-derived DI-like segments share internal deletions of the same segments. The presence of identical DI-like RNAs in patients linked by direct contact is compatible with transmission between them. The functional role of DI-like RNAs in natural infections remains to be established.
authors.affiliation: Department of Computational & Systems Biology, Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Kazima
authors.initials: K
authors.lastname: Saira
authors.forename: Xudong
authors.initials: X
authors.lastname: Lin
authors.forename: Jay V
authors.initials: JV
authors.lastname: DePasse
authors.forename: Rebecca
authors.initials: R
authors.lastname: Halpin
authors.forename: Alan
authors.initials: A
authors.lastname: Twaddle
authors.forename: Timothy
authors.initials: T
authors.lastname: Stockwell
authors.forename: Brian
authors.initials: B
authors.lastname: Angus
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cozzi-Lepri
authors.forename: Marina
authors.initials: M
authors.lastname: Delfino
authors.forename: Vivien
authors.initials: V
authors.lastname: Dugan
authors.forename: Dominic E
authors.initials: DE
authors.lastname: Dwyer
authors.forename: Matthew
authors.initials: M
authors.lastname: Freiberg
authors.forename: Andrzej
authors.initials: A
authors.lastname: Horban
authors.forename: Marcelo
authors.initials: M
authors.lastname: Losso
authors.forename: Ruth
authors.initials: R
authors.lastname: Lynfield
authors.forename: Deborah N
authors.initials: DN
authors.lastname: Wentworth
authors.forename: Edward C
authors.initials: EC
authors.lastname: Holmes
authors.forename: Richard
authors.initials: R
authors.lastname: Davey
authors.forename: David E
authors.initials: DE
authors.lastname: Wentworth
authors.forename: Elodie
authors.initials: E
authors.lastname: Ghedin
mesh_terms: D001483:Base Sequence; D003001:Cloning, Molecular; D019295:Computational Biology; D003673:Defective Viruses / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics*; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
chemical_list: D012367:RNA, Viral