Amino acid changes in hemagglutinin contribute to the replication of oseltamivir-resistant H1N1 influenza viruses.
Oseltamivir-resistant H1N1 influenza viruses emerged in 2007 to 2008 and have subsequently circulated widely. However, prior to 2007 to 2008, viruses possessing the neuraminidase (NA) H274Y mutation, which confers oseltamivir resistance, generally had low growth capability. NA mutations that compensate for the deleterious effect of the NA H274Y mutation have since been identified. Given the importance of the functional balance between hemagglutinin (HA) and NA, we focused on amino acid changes in HA. Reverse genetic analysis showed that a mutation at residue 82, 141, or 189 of the HA protein promotes virus replication in the presence of the NA H274Y mutation. Our findings thus identify HA mutations that contributed to the replacement of the oseltamivir-sensitive viruses of 2007 to 2008.
Center for Infectious Diseases, Graduate School of Medicine, Kobe University, Kobe, Hyogo, Japan.
Teridah Ernala
TE
Ginting
Kyoko
K
Shinya
Yukihiro
Y
Kyan
Akiko
A
Makino
Naomi
N
Matsumoto
Satoko
S
Kaneda
Yoshihiro
Y
Kawaoka
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000187:drug effects; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D024882:Drug Resistance, Viral / Q000187:drug effects; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000145:classification / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D007251:Influenza, Human / Q000821:virology*; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009439:Neuraminidase / Q000235:genetics / Q000378:metabolism; D053139:Oseltamivir / Q000494:pharmacology*; D010802:Phylogeny; D016415:Sequence Alignment; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; C543345:H1N1 virus hemagglutinin; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D014764:Viral Proteins; D053139:Oseltamivir; C487630:NA protein, influenza A virus; D009439:Neuraminidase