title: Impact of a large deletion in the neuraminidase protein identified in a laninamivir-selected influenza A/Brisbane/10/2007 (H3N2) variant on viral fitness in vitro and in ferrets.
abstract: Viral fitness of a laninamivir-selected influenza A/Brisbane/10/2007-like (H3N2) isolate (LRVp9) containing a 237-amino acid neuraminidase deletion and a P194L hemagglutinin mutation was evaluated in vitro and in ferrets. LRVp9 and the wild-type (WT) virus showed comparable replication kinetics in MDCK-ST6GalI cells. Cultured virus was recovered between days 2 and 5 post-infection in nasal washes (NW) from the 4 WT-infected ferrets whereas no virus was recovered from the LRVp9-infected animals. There was a ≥1 log reduction in viral RNA copies/μl of NW for LRVp9 compared to WT at most time points. The large neuraminidase deletion compromises viral infectivity in vivo.
authors.affiliation: CHU de Quebec Research Center (CHUL) and Laval University, Québec City, QC, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Ann
authors.affiliation: CHU de Quebec Research Center (CHUL) and Laval University, Québec City, QC, Canada.
authors.forename: Yacine
authors.initials: Y
authors.lastname: Abed
authors.affiliation: GSK Vaccines, Laval, QC, Canada.
authors.forename: Edith
authors.initials: E
authors.lastname: Beaulieu
authors.affiliation: CHU de Quebec Research Center (CHUL) and Laval University, Québec City, QC, Canada.
authors.forename: Xavier
authors.initials: X
authors.lastname: Bouhy
authors.affiliation: GSK Vaccines, Laval, QC, Canada.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Joly
authors.affiliation: GSK Vaccines, Laval, QC, Canada.
authors.forename: Karen
authors.initials: K
authors.lastname: Dubé
authors.affiliation: CHU de Quebec Research Center (CHUL) and Laval University, Québec City, QC, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Carbonneau
authors.affiliation: CHU de Quebec Research Center (CHUL) and Laval University, Québec City, QC, Canada.
authors.forename: Marie-Eve
authors.initials: ME
authors.lastname: Hamelin
authors.affiliation: GSK Vaccines, Laval, QC, Canada.
authors.forename: Corey
authors.initials: C
authors.lastname: Mallett
authors.affiliation: CHU de Quebec Research Center (CHUL) and Laval University, Québec City, QC, Canada.
authors.forename: Guy
authors.initials: G
authors.lastname: Boivin
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D024882:Drug Resistance, Viral / Q000235:genetics; D005289:Ferrets / Q000821:virology*; D017353:Gene Deletion; D056084:Genetic Fitness; D006146:Guanidines; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D007251:Influenza, Human / Q000821:virology; D009154:Mutation; D009439:Neuraminidase / Q000172:deficiency / Q000235:genetics*; D009976:Orthomyxoviridae Infections / Q000821:virology*; D011714:Pyrans; D012367:RNA, Viral; D012794:Sialic Acids; D014779:Virus Replication / Q000187:drug effects; D053243:Zanamivir / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D006146:Guanidines; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011714:Pyrans; D012367:RNA, Viral; D012794:Sialic Acids; C546918:laninamivir; D009439:Neuraminidase; D053243:Zanamivir
keywords: A(H3N2); deletion; influenza; neuraminidase; resistance