tetano
Editor, Senior Moderator
J Virol. 2014 Sep 24. pii: JVI.02475-14. [Epub ahead of print]
DnaJA1/Hsp40 is co-opted by influenza A virus to enhance its viral RNA polymerase activity.
Cao M1, Wei C1, Zhao L1, Wang J1, Jia Q1, Wang X1, Jin Q2, Deng T2.
Author information
Abstract
The RNA-dependent RNA polymerase (RdRp) of influenza A virus is a heterotrimeric complex composed by PB1, PB2 and PA subunits. The interplay between host factors and the three subunits of the RdRp is critical to enable viral RNA synthesis to occur in the nucleus of infected cells. In this report, we newly identified a host factor DnaJA1, a member of the type I DnaJ/Hsp40 family, acting as a positive regulator for influenza virus replication. We found that DnaJA1 associates with PB2 and PA subunits and enhances viral RNA synthesis both in vivo and in vitro. Moreover, DnaJA1 could be translocated from cytoplasm into the nucleus upon influenza virus infection. The translocation of DnaJA1 is specifically accompanied by the PB1-PA nuclear import. Interestingly, we observed that the effect of DnaJA1 on viral RNA synthesis is mainly dependent on its C-terminal substrate-binding domain but not on its typical J-domain, while the J-domain normally mediates the Hsp70-DnaJ interaction required for regulating Hsp70 ATPase activity. Therefore, we propose that DnaJA1 is co-opted by the influenza A virus to entre nucleus and to enhance its RNA polymerase activity in an Hsp70 cochaperone-independent manner.
IMPORTANCE:
The interplay between host factors and influenza virus RNA polymerase plays a critical role in determining virus pathogenicity and host adaption. In this report, we newly identified a host protein DnaJA1/Hsp40 that is co-opted by influenza A virus RNA polymerase to enhance its viral RNA synthesis in the nucleus of infected cells. We found that DnaJA1 associates with both PB2 and PA subunits and translocates into nucleus along with the nuclear import of PB1-PA dimer during influenza virus replication. Interestingly, the effect of DnaJA1 is mainly dependent on its C-terminal substrate-binding domain but not on its typical J-domain that is required for its Hsp70 cochaperone function. To our knowledge, this is the first report on a member of Hsp40s that is specifically involved in regulating influenza virus RNA polymerase. Targeting the interactions between polymerase subunits and DnaJA1 may provide a novel strategy to develop antiviral drugs.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
25253355
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25253355
DnaJA1/Hsp40 is co-opted by influenza A virus to enhance its viral RNA polymerase activity.
Cao M1, Wei C1, Zhao L1, Wang J1, Jia Q1, Wang X1, Jin Q2, Deng T2.
Author information
Abstract
The RNA-dependent RNA polymerase (RdRp) of influenza A virus is a heterotrimeric complex composed by PB1, PB2 and PA subunits. The interplay between host factors and the three subunits of the RdRp is critical to enable viral RNA synthesis to occur in the nucleus of infected cells. In this report, we newly identified a host factor DnaJA1, a member of the type I DnaJ/Hsp40 family, acting as a positive regulator for influenza virus replication. We found that DnaJA1 associates with PB2 and PA subunits and enhances viral RNA synthesis both in vivo and in vitro. Moreover, DnaJA1 could be translocated from cytoplasm into the nucleus upon influenza virus infection. The translocation of DnaJA1 is specifically accompanied by the PB1-PA nuclear import. Interestingly, we observed that the effect of DnaJA1 on viral RNA synthesis is mainly dependent on its C-terminal substrate-binding domain but not on its typical J-domain, while the J-domain normally mediates the Hsp70-DnaJ interaction required for regulating Hsp70 ATPase activity. Therefore, we propose that DnaJA1 is co-opted by the influenza A virus to entre nucleus and to enhance its RNA polymerase activity in an Hsp70 cochaperone-independent manner.
IMPORTANCE:
The interplay between host factors and influenza virus RNA polymerase plays a critical role in determining virus pathogenicity and host adaption. In this report, we newly identified a host protein DnaJA1/Hsp40 that is co-opted by influenza A virus RNA polymerase to enhance its viral RNA synthesis in the nucleus of infected cells. We found that DnaJA1 associates with both PB2 and PA subunits and translocates into nucleus along with the nuclear import of PB1-PA dimer during influenza virus replication. Interestingly, the effect of DnaJA1 is mainly dependent on its C-terminal substrate-binding domain but not on its typical J-domain that is required for its Hsp70 cochaperone function. To our knowledge, this is the first report on a member of Hsp40s that is specifically involved in regulating influenza virus RNA polymerase. Targeting the interactions between polymerase subunits and DnaJA1 may provide a novel strategy to develop antiviral drugs.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
25253355
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25253355