tetano
Editor, Senior Moderator
J Gen Virol. 2011 Nov 16. [Epub ahead of print]
Amino acids 473V and 598P of PB1 from an avian origin influenza A virus contribute to polymerase activity especially in mammalian cells.
Xu C, Hu WB, Xu K, He YX, Wang TY, Chen Z, Li TX, Liu JH, Buchy P, Sun B.
Source
Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai Institue of Pasteur;
Abstract
It has been reported that the avian-origin PB1 protein (avian PB1) enhances influenza A virus polymerase activity in mammalian cells when it replaces the human-origin PB1 protein (human PB1). Characterization of the amino acid residues that contribute to this enhancement is needed. In this study, we found that PB1 protein from an avian origin influenza A virus (A/Cambodia/P0322095/2005, H5N1 [Cam]) could enhance the polymerase activity of an attenuated human isolated virus A/WSN/33 carrying the PB2 K627E mutation (WSN627E) in vitro. Furthermore, we identified 473 valine (V) and 598 proline (P) in the Cam PB1 as the residues responsible for this enhanced activity. Results from recombinant virus experiments demonstrate the contribution of PB1 amino acids 473V and 598P to polymerase activity in mammalian cells and in mice. Interestingly, the 473V is conserved in pH1N1 viruses from the 2009 pandemic. Substitution of the 473V by Leucine (L) in pH1N1 PB1 led to a decreased viral polymerase activity and a lower growth rate in mammalian cells, suggesting that PB1 amino acid 473V also plays a role in maintaining efficient viral replication of the pH1N1 virus. Thus, we conclude that two amino acids in avian-origin PB1, 473V and 598P, contribute to the polymerase activity of the H5N1 virus especially in mammalian cells, and that 473V in PB1 also contributes to efficient replication of the pH1N1 strain.
PMID:
22090209
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22090209
Amino acids 473V and 598P of PB1 from an avian origin influenza A virus contribute to polymerase activity especially in mammalian cells.
Xu C, Hu WB, Xu K, He YX, Wang TY, Chen Z, Li TX, Liu JH, Buchy P, Sun B.
Source
Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai Institue of Pasteur;
Abstract
It has been reported that the avian-origin PB1 protein (avian PB1) enhances influenza A virus polymerase activity in mammalian cells when it replaces the human-origin PB1 protein (human PB1). Characterization of the amino acid residues that contribute to this enhancement is needed. In this study, we found that PB1 protein from an avian origin influenza A virus (A/Cambodia/P0322095/2005, H5N1 [Cam]) could enhance the polymerase activity of an attenuated human isolated virus A/WSN/33 carrying the PB2 K627E mutation (WSN627E) in vitro. Furthermore, we identified 473 valine (V) and 598 proline (P) in the Cam PB1 as the residues responsible for this enhanced activity. Results from recombinant virus experiments demonstrate the contribution of PB1 amino acids 473V and 598P to polymerase activity in mammalian cells and in mice. Interestingly, the 473V is conserved in pH1N1 viruses from the 2009 pandemic. Substitution of the 473V by Leucine (L) in pH1N1 PB1 led to a decreased viral polymerase activity and a lower growth rate in mammalian cells, suggesting that PB1 amino acid 473V also plays a role in maintaining efficient viral replication of the pH1N1 virus. Thus, we conclude that two amino acids in avian-origin PB1, 473V and 598P, contribute to the polymerase activity of the H5N1 virus especially in mammalian cells, and that 473V in PB1 also contributes to efficient replication of the pH1N1 strain.
PMID:
22090209
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22090209