tetano
Editor, Senior Moderator
J Virol. 2015 Sep 16. pii: JVI.01576-15. [Epub ahead of print]
[h=1]RIG-I Signaling Is Essential For Influenza B Virus-Induced Rapid Interferon Gene Expression.[/h] M?kel? SM[SUP]1[/SUP], ?sterlund P[SUP]2[/SUP], Westenius V[SUP]2[/SUP], Latvala S[SUP]2[/SUP], Diamond MS[SUP]3[/SUP], Gale M Jr[SUP]4[/SUP], Julkunen I[SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza B virus causes annual epidemics and along with influenza A virus accounts for substantial disease and economic burden throughout the world. Influenza B infects only humans and some marine mammals and is not responsible for pandemics possibly due to a very low frequency of reassortation and a lower evolutionary rate compared to influenza A virus. Influenza B virus has been less studied than influenza A and thus a comparison of influenza A and B virus infection mechanisms may provide new insight into virus-host interactions. Here we analyzed the early events in influenza B virus infection and interferon (IFN) gene expression in human monocyte-derived macrophages and dendritic cells. We show that influenza B virus induces IRF3 activation and IFN-λ1 gene expression with a faster kinetics compared to influenza A virus without a requirement for viral protein synthesis or replication. Influenza B virus-induced activation of IRF3 required the fusion of viral and endosomal membranes and nuclear accumulation of IRF3 and viral NP occurred concurrently. In comparison, immediate early IRF3 activation was not observed in influenza A virus-infected macrophages. Experiments with RIG-I, MDA5 and RIG-I/MDA5 deficient mouse fibroblasts showed that RIG-I is the critical pattern recognition receptor needed for the influenza B virus-induced activation of IRF3. Our results show that innate immune mechanisms are activated immediately after influenza B virus entry through the endocytic pathway, whereas influenza A virus avoids the early IRF3 activation and IFN gene induction.
[h=4]IMPORTANCE:[/h] Recently, a great deal of interest has been paid on identifying the ligands for RIG-I under a natural infection as many of the previous studies have been based on transfecting the cells with different types of viral or synthetic RNA structures. We shed light on this question by analyzing the earliest step in innate immune recognition of influenza B virus by human macrophages. We show that influenza B virus induces IRF3 activation leading to the IFN gene expression after the viral vRNPs are released to the cytosol and are recognized by RIG-I receptor meaning that already the incoming influenza B virus is able to activate IFN gene expression. In contrast, influenza A (H3N2) virus failed to activate IRF3 at very early times of infection suggesting that there are differences in the innate immune recognition between influenza A and B viruses.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 26378160 [PubMed - as supplied by publisher]
[h=1]RIG-I Signaling Is Essential For Influenza B Virus-Induced Rapid Interferon Gene Expression.[/h] M?kel? SM[SUP]1[/SUP], ?sterlund P[SUP]2[/SUP], Westenius V[SUP]2[/SUP], Latvala S[SUP]2[/SUP], Diamond MS[SUP]3[/SUP], Gale M Jr[SUP]4[/SUP], Julkunen I[SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza B virus causes annual epidemics and along with influenza A virus accounts for substantial disease and economic burden throughout the world. Influenza B infects only humans and some marine mammals and is not responsible for pandemics possibly due to a very low frequency of reassortation and a lower evolutionary rate compared to influenza A virus. Influenza B virus has been less studied than influenza A and thus a comparison of influenza A and B virus infection mechanisms may provide new insight into virus-host interactions. Here we analyzed the early events in influenza B virus infection and interferon (IFN) gene expression in human monocyte-derived macrophages and dendritic cells. We show that influenza B virus induces IRF3 activation and IFN-λ1 gene expression with a faster kinetics compared to influenza A virus without a requirement for viral protein synthesis or replication. Influenza B virus-induced activation of IRF3 required the fusion of viral and endosomal membranes and nuclear accumulation of IRF3 and viral NP occurred concurrently. In comparison, immediate early IRF3 activation was not observed in influenza A virus-infected macrophages. Experiments with RIG-I, MDA5 and RIG-I/MDA5 deficient mouse fibroblasts showed that RIG-I is the critical pattern recognition receptor needed for the influenza B virus-induced activation of IRF3. Our results show that innate immune mechanisms are activated immediately after influenza B virus entry through the endocytic pathway, whereas influenza A virus avoids the early IRF3 activation and IFN gene induction.
[h=4]IMPORTANCE:[/h] Recently, a great deal of interest has been paid on identifying the ligands for RIG-I under a natural infection as many of the previous studies have been based on transfecting the cells with different types of viral or synthetic RNA structures. We shed light on this question by analyzing the earliest step in innate immune recognition of influenza B virus by human macrophages. We show that influenza B virus induces IRF3 activation leading to the IFN gene expression after the viral vRNPs are released to the cytosol and are recognized by RIG-I receptor meaning that already the incoming influenza B virus is able to activate IFN gene expression. In contrast, influenza A (H3N2) virus failed to activate IRF3 at very early times of infection suggesting that there are differences in the innate immune recognition between influenza A and B viruses.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 26378160 [PubMed - as supplied by publisher]