tetano
Editor, Senior Moderator
Nat Commun. 2014 Oct 7;5:5021. doi: 10.1038/ncomms6021.
Novel residues in avian influenza virus PB2 protein affect virulence in mammalian hosts.
Fan S1, Hatta M1, Kim JH1, Halfmann P1, Imai M1, Macken CA2, Le MQ3, Nguyen T4, Neumann G1, Kawaoka Y5.
Author information
Abstract
Highly pathogenic avian H5N1 influenza viruses have sporadically transmitted to humans causing high mortality. The mechanistic basis for adaptation is still poorly understood, although several residues in viral protein PB2 are known to be important for this event. Here, we demonstrate that three residues, 147T, 339T and 588T, in PB2 play critical roles in the virulence of avian H5N1 influenza viruses in a mammalian host in vitro and in vivo and, together, result in a phenotype comparable to that conferred by the previously known PB2-627K mutation with respect to virus polymerase activity. A virus with the three residues and 627K in PB2, as has been isolated from a lethal human case, is more pathogenic than viruses with only the three residues or 627K in PB2. Importantly, H5N1 viruses bearing the former three PB2 residues have circulated widely in recent years in avian species in nature.
PMID:
25289523
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25289523
Novel residues in avian influenza virus PB2 protein affect virulence in mammalian hosts.
Fan S1, Hatta M1, Kim JH1, Halfmann P1, Imai M1, Macken CA2, Le MQ3, Nguyen T4, Neumann G1, Kawaoka Y5.
Author information
Abstract
Highly pathogenic avian H5N1 influenza viruses have sporadically transmitted to humans causing high mortality. The mechanistic basis for adaptation is still poorly understood, although several residues in viral protein PB2 are known to be important for this event. Here, we demonstrate that three residues, 147T, 339T and 588T, in PB2 play critical roles in the virulence of avian H5N1 influenza viruses in a mammalian host in vitro and in vivo and, together, result in a phenotype comparable to that conferred by the previously known PB2-627K mutation with respect to virus polymerase activity. A virus with the three residues and 627K in PB2, as has been isolated from a lethal human case, is more pathogenic than viruses with only the three residues or 627K in PB2. Importantly, H5N1 viruses bearing the former three PB2 residues have circulated widely in recent years in avian species in nature.
PMID:
25289523
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25289523