tetano
Editor, Senior Moderator
J Virol. 2015 Jan 21. pii: JVI.03328-14. [Epub ahead of print]
[h=1]Identification of PB2 mutations responsible for the efficient replication of H5N1 influenza viruses in human lung epithelial cells.[/h] Yamaji R[SUP]1[/SUP], Yamada S[SUP]2[/SUP], Le MQ[SUP]3[/SUP], Li C[SUP]4[/SUP], Chen H[SUP]4[/SUP], Qurnianingsih E[SUP]5[/SUP], Nidom CA[SUP]5[/SUP], Ito M[SUP]1[/SUP], Sakai-Tagawa Y[SUP]1[/SUP], Kawaoka Y[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Highly pathogenic H5N1 avian influenza viruses have caused outbreaks among poultry worldwide, resulting in sporadic infections in humans, approximately 60% mortality of which have been fatal. However, efficient transmission of H5N1 viruses among humans has yet to occur, suggesting that further adaptation of H5N1 viruses to humans is required for their efficient transmission among humans. Viral determinants for efficient replication in humans are currently poorly understood. Here, we report that the polymerase PB2 protein of an H5N1 influenza virus isolated from a human in Vietnam (A/Vietnam/UT36285/2010, 36285) increased the growth ability of an avian H5N1 virus (A/wild bird/Anhui/82/2005, Wb/AH82) in human lung epithelial A549 cells (although, the reassortant virus did not replicate more efficiently than human 36285 virus). Furthermore, we demonstrate that amino acid residues at positions 249, 309, and 339 of the PB2 protein from this human isolate were responsible for its efficient replication in A549 cells. PB2-249G and 339M, which are found in the human H5N1 virus, are rare in H5N1 viruses from both human and avian sources. Interestingly, PB2-249G is found in over 30% of human seasonal H3N2 viruses, which suggests that H5N1 viruses may replicate well in human cells when they acquire this mutation. Our data are of value to H5N1 virus surveillance.
[h=4]IMPORTANCE:[/h] Highly pathogenic H5N1 avian influenza viruses must acquire mutations to overcome the species barrier between avian species and humans. When H5N1 viruses replicate in human respiratory cells, they can acquire amino acid mutations that allow them to adapt to humans through continuous selective pressure. Several amino acid mutations have been shown to be advantageous for virus adaptation to mammalian hosts. Here, we found that amino acid changes at positions 249, 309, and 339 of PB2 contribute to efficient replication of avian H5N1 viruses in human lung cells. These findings are beneficial for evaluating the pandemic risk of circulating avian viruses and for further functional analysis of PB2.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 25609813 [PubMed - as supplied by publisher]
[h=1]Identification of PB2 mutations responsible for the efficient replication of H5N1 influenza viruses in human lung epithelial cells.[/h] Yamaji R[SUP]1[/SUP], Yamada S[SUP]2[/SUP], Le MQ[SUP]3[/SUP], Li C[SUP]4[/SUP], Chen H[SUP]4[/SUP], Qurnianingsih E[SUP]5[/SUP], Nidom CA[SUP]5[/SUP], Ito M[SUP]1[/SUP], Sakai-Tagawa Y[SUP]1[/SUP], Kawaoka Y[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Highly pathogenic H5N1 avian influenza viruses have caused outbreaks among poultry worldwide, resulting in sporadic infections in humans, approximately 60% mortality of which have been fatal. However, efficient transmission of H5N1 viruses among humans has yet to occur, suggesting that further adaptation of H5N1 viruses to humans is required for their efficient transmission among humans. Viral determinants for efficient replication in humans are currently poorly understood. Here, we report that the polymerase PB2 protein of an H5N1 influenza virus isolated from a human in Vietnam (A/Vietnam/UT36285/2010, 36285) increased the growth ability of an avian H5N1 virus (A/wild bird/Anhui/82/2005, Wb/AH82) in human lung epithelial A549 cells (although, the reassortant virus did not replicate more efficiently than human 36285 virus). Furthermore, we demonstrate that amino acid residues at positions 249, 309, and 339 of the PB2 protein from this human isolate were responsible for its efficient replication in A549 cells. PB2-249G and 339M, which are found in the human H5N1 virus, are rare in H5N1 viruses from both human and avian sources. Interestingly, PB2-249G is found in over 30% of human seasonal H3N2 viruses, which suggests that H5N1 viruses may replicate well in human cells when they acquire this mutation. Our data are of value to H5N1 virus surveillance.
[h=4]IMPORTANCE:[/h] Highly pathogenic H5N1 avian influenza viruses must acquire mutations to overcome the species barrier between avian species and humans. When H5N1 viruses replicate in human respiratory cells, they can acquire amino acid mutations that allow them to adapt to humans through continuous selective pressure. Several amino acid mutations have been shown to be advantageous for virus adaptation to mammalian hosts. Here, we found that amino acid changes at positions 249, 309, and 339 of PB2 contribute to efficient replication of avian H5N1 viruses in human lung cells. These findings are beneficial for evaluating the pandemic risk of circulating avian viruses and for further functional analysis of PB2.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 25609813 [PubMed - as supplied by publisher]