title: In vitro characterization of naturally occurring influenza H3NA- viruses lacking the NA gene segment: toward a new mechanism of viral resistance?
abstract: Among a panel of 788 clinical influenza H3N2 isolates, two isolates were characterized by an oseltamivir-resistant phenotype linked to the absence of any detectable NA activity. Here, we established that the two H3NA- isolates lack any detectable full-length NA segment, and one of these could be rescued by reverse genetics in the absence of any NA segment sequence. We found that the absence of NA segment induced a moderate growth defect of the H3NA- viruses as on cultured cells. The glycoproteins density at the surface of H3NA- virions was unchanged as compared to H3N2 virions. The HA protein as well as residues 188 and 617 of the PB1 protein were shown to be strong determinants of the ability of H3NA- viruses to grow in the absence of the NA segment. The significance of these findings about naturally occurring seven-segment influenza A viruses is discussed.
authors.affiliation: Université de Lyon, F-69000, Lyon, France. vincent.moules@recherche.univ-lyon1.fr
authors.forename: V
authors.initials: V
authors.lastname: Moules
authors.forename: O
authors.initials: O
authors.lastname: Ferraris
authors.forename: O
authors.initials: O
authors.lastname: Terrier
authors.forename: E
authors.initials: E
authors.lastname: Giudice
authors.forename: M
authors.initials: M
authors.lastname: Yver
authors.forename: J P
authors.initials: JP
authors.lastname: Rolland
authors.forename: M
authors.initials: M
authors.lastname: Bouscambert-Duchamp
authors.forename: C
authors.initials: C
authors.lastname: Bergeron
authors.forename: M
authors.initials: M
authors.lastname: Ottmann
authors.forename: E
authors.initials: E
authors.lastname: Fournier
authors.forename: A
authors.initials: A
authors.lastname: Traversier
authors.forename: C
authors.initials: C
authors.lastname: Boule
authors.forename: A
authors.initials: A
authors.lastname: Rivoire
authors.forename: Y
authors.initials: Y
authors.lastname: Lin
authors.forename: A
authors.initials: A
authors.lastname: Hay
authors.forename: M
authors.initials: M
authors.lastname: Valette
authors.forename: R
authors.initials: R
authors.lastname: Marquet
authors.forename: M
authors.initials: M
authors.lastname: Rosa-Calatrava
authors.forename: N
authors.initials: N
authors.lastname: Naffakh
authors.forename: G
authors.initials: G
authors.lastname: Schoehn
authors.forename: D
authors.initials: D
authors.lastname: Thomas
authors.forename: B
authors.initials: B
authors.lastname: Lina
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D002460:Cell Line; D020285:Cryoelectron Microscopy; D004285:Dogs; D024882:Drug Resistance, Viral / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D009980:Influenza A virus / Q000187:drug effects / Q000201:enzymology / Q000235:genetics* / Q000502:physiology; D008958:Models, Molecular; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics*; D053139:Oseltamivir / Q000494:pharmacology; D011487:Protein Conformation; D016415:Sequence Alignment; D014771:Virion / Q000648:ultrastructure; D014779:Virus Replication / Q000502:physiology*
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D053139:Oseltamivir; D009439:Neuraminidase