Characterization of drug-resistant recombinant influenza A/H1N1 viruses selected in vitro with peramivir and zanamivir.
There is a limited information with regard to the neuraminidase (NA) mutations conferring resistance to peramivir and zanamivir in the influenza N1 background. In this study, an influenza A/WSN/33 (H1N1) recombinant virus was passaged under peramivir or zanamivir pressure. The peramivir-selected variant had a H274Y mutation in the neuraminidase (NA) gene conferring resistance to peramivir and oseltamivir but susceptibility to zanamivir. The zanamivir-selected variant had a massive deletion in the region encoding the NA active center and an A200T hemagglutinin mutation. This variant exhibited reduced susceptibility to zanamivir with a drug-dependent phenotype.
Baz
Mariana
M
Research Center in Infectious Diseases of the CHUQ-CHUL and Laval University, Québec City, Que., Canada.
Abed
Yacine
Y
Boivin
Guy
G
D000146:Acids, Carbocyclic; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D003517:Cyclopentanes / Q000494:pharmacology*; D004285:Dogs; D024882:Drug Resistance, Viral / Q000235:genetics*; D006146:Guanidines / Q000494:pharmacology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000235:genetics; D009154:Mutation; D020125:Mutation, Missense; D009439:Neuraminidase / Q000235:genetics; D053139:Oseltamivir / Q000494:pharmacology; D012641:Selection, Genetic; D017384:Sequence Deletion / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics; D053243:Zanamivir / Q000494:pharmacology*
D000146:Acids, Carbocyclic; D000998:Antiviral Agents; D003517:Cyclopentanes; D006146:Guanidines; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D014764:Viral Proteins; D053139:Oseltamivir; C487630:NA protein, influenza A virus; D009439:Neuraminidase; D053243:Zanamivir; C414210:peramivir