tetano
Editor, Senior Moderator
J Virol. 2014 Jul 16. pii: JVI.01564-14. [Epub ahead of print]
Amino acid substitutions in PB1 of avian influenza viruses influence pathogenicity and transmissibility in chickens.
Suzuki Y1, Uchida Y2, Tanikawa T1, Maeda N1, Takemae N2, Saito T3.
Author information
Abstract
Amino acid substitutions in PB1 were introduced to characterize the interaction between polymerase activity and pathogenicity. Previously, we demonstrated that pathogenicity of the highly pathogenic avian influenza virus (HPAIV) H5N1 in chickens is regulated by the PB1 gene, using recombinant viruses containing the hemagglutinin (HA) and neuraminidase genes from an H5N1 strain, and other internal genes from two low-pathogenicity avian influenza viruses isolated from chicken (LP) and wild bird (WB) hosts (Y. Uchida et al., J. Virol. 86: 2686-2695, 2012, doi: 10.1128/JVI.06374-11). In this study, we introduced a C38Y substitution into PB1 of WB and demonstrated that this substitution increased polymerase activity in vitro in DF-1 cells, as well as pathogenicity of the recombinant viruses in chickens. The V14A substitution in PB1 of LP reduced polymerase activity, but did not affect pathogenicity in chickens. Interestingly, the V14A substitution reduced viral shedding and transmissibility. These studies demonstrate that increasing polymerase activity directly correlates with enhanced pathogenicity, while decreased polymerase activity does not always correlate with pathogenicity and requires further analysis.
IMPORTANCE:
We identified 2 novel amino acid substitutions in the PB1 gene of avian influenza virus that affect viral characteristics of highly pathogenic avian influenza virus (HPAIV) H5N1, such as viral replication and polymerase activity in vitro and pathogenicity and transmissibly in chickens. Amino acid substitution at residue 38 in PB1 directly affected pathogenicity in chickens, and was associated with changes in polymerase activity in vitro. Substitution at residue 14 reduced polymerase activity in vitro, while its effects on pathogenicity and transmissibility depended on the constellation of the internal genes.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
25031333
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25031333
Amino acid substitutions in PB1 of avian influenza viruses influence pathogenicity and transmissibility in chickens.
Suzuki Y1, Uchida Y2, Tanikawa T1, Maeda N1, Takemae N2, Saito T3.
Author information
Abstract
Amino acid substitutions in PB1 were introduced to characterize the interaction between polymerase activity and pathogenicity. Previously, we demonstrated that pathogenicity of the highly pathogenic avian influenza virus (HPAIV) H5N1 in chickens is regulated by the PB1 gene, using recombinant viruses containing the hemagglutinin (HA) and neuraminidase genes from an H5N1 strain, and other internal genes from two low-pathogenicity avian influenza viruses isolated from chicken (LP) and wild bird (WB) hosts (Y. Uchida et al., J. Virol. 86: 2686-2695, 2012, doi: 10.1128/JVI.06374-11). In this study, we introduced a C38Y substitution into PB1 of WB and demonstrated that this substitution increased polymerase activity in vitro in DF-1 cells, as well as pathogenicity of the recombinant viruses in chickens. The V14A substitution in PB1 of LP reduced polymerase activity, but did not affect pathogenicity in chickens. Interestingly, the V14A substitution reduced viral shedding and transmissibility. These studies demonstrate that increasing polymerase activity directly correlates with enhanced pathogenicity, while decreased polymerase activity does not always correlate with pathogenicity and requires further analysis.
IMPORTANCE:
We identified 2 novel amino acid substitutions in the PB1 gene of avian influenza virus that affect viral characteristics of highly pathogenic avian influenza virus (HPAIV) H5N1, such as viral replication and polymerase activity in vitro and pathogenicity and transmissibly in chickens. Amino acid substitution at residue 38 in PB1 directly affected pathogenicity in chickens, and was associated with changes in polymerase activity in vitro. Substitution at residue 14 reduced polymerase activity in vitro, while its effects on pathogenicity and transmissibility depended on the constellation of the internal genes.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
25031333
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25031333