tetano
Editor, Senior Moderator
J Virol. 2014 Jun 4. pii: JVI.00422-14. [Epub ahead of print]
PB2 Mutations D701N and S714R Promote Adaptation of an Influenza H5N1 Virus to a Mammalian Host.
Czudai-Matwich V1, Otte A2, Matrosovich M1, Gabriel G2, Klenk HD3.
Author information
Abstract
Mutation D701N in the PB2 protein is known to play a prominent role in the adaptation of avian influenza A viruses to mammalian hosts. In contrast, little is known about mutations S714I and S714R located nearby, that have been observed in some avian influenza viruses highly pathogenic for mammals. We have generated recombinant H5N1 viruses with PB2 displaying the avian signature 701D or the mammalian signature 701N and serine, isoleucine and arginine at position 714, and compared them for polymerase activity and virus growth in avian and mammalian cells as well as for pathogenicity in mice. Mutation D701N led to an increase in polymerase activity and replication efficiency in mammalian cells and in mouse pathogenicity, and this increase was significantly enhanced when mutation D701N was combined with mutation S714R. Stimulation by mutation S714I was less distinct. These observations indicate that PB2 mutation S714R, in combination with the mammalian signature at position 701, has the potential to promote adaptation of an H5N1 virus to a mammalian host.
IMPORTANCE:
Influenza A/H5N1 viruses are avian pathogens that have pandemic potential, since they are spread over large parts of Asia, Africa, and Europe and are occasionally transmitted to humans. It is therefore of high scientific interest to understand the mechanisms determining host specificity and pathogenicity of these viruses. It is well known that the PB2 subunit of the viral polymerase is an important host range determinant and that PB2 mutation D701N plays an important role in virus adaptation to mammalian cells. In the present study we show that mutation S714R is also involved in adaptation and that it co-operates with D701N in exposing a nuclear localization signal that mediates importin-α binding and entry of PB2 into the nucleus where virus replication and transcription take place.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
24899203
[PubMed - as supplied by publisher]
Free full text
http://www.ncbi.nlm.nih.gov/pubmed/24899203
PB2 Mutations D701N and S714R Promote Adaptation of an Influenza H5N1 Virus to a Mammalian Host.
Czudai-Matwich V1, Otte A2, Matrosovich M1, Gabriel G2, Klenk HD3.
Author information
Abstract
Mutation D701N in the PB2 protein is known to play a prominent role in the adaptation of avian influenza A viruses to mammalian hosts. In contrast, little is known about mutations S714I and S714R located nearby, that have been observed in some avian influenza viruses highly pathogenic for mammals. We have generated recombinant H5N1 viruses with PB2 displaying the avian signature 701D or the mammalian signature 701N and serine, isoleucine and arginine at position 714, and compared them for polymerase activity and virus growth in avian and mammalian cells as well as for pathogenicity in mice. Mutation D701N led to an increase in polymerase activity and replication efficiency in mammalian cells and in mouse pathogenicity, and this increase was significantly enhanced when mutation D701N was combined with mutation S714R. Stimulation by mutation S714I was less distinct. These observations indicate that PB2 mutation S714R, in combination with the mammalian signature at position 701, has the potential to promote adaptation of an H5N1 virus to a mammalian host.
IMPORTANCE:
Influenza A/H5N1 viruses are avian pathogens that have pandemic potential, since they are spread over large parts of Asia, Africa, and Europe and are occasionally transmitted to humans. It is therefore of high scientific interest to understand the mechanisms determining host specificity and pathogenicity of these viruses. It is well known that the PB2 subunit of the viral polymerase is an important host range determinant and that PB2 mutation D701N plays an important role in virus adaptation to mammalian cells. In the present study we show that mutation S714R is also involved in adaptation and that it co-operates with D701N in exposing a nuclear localization signal that mediates importin-α binding and entry of PB2 into the nucleus where virus replication and transcription take place.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
24899203
[PubMed - as supplied by publisher]
Free full text
http://www.ncbi.nlm.nih.gov/pubmed/24899203