tetano
Editor, Senior Moderator
J Virol. 2016 Apr 27. pii: JVI.00549-16. [Epub ahead of print]
[h=1]Robust Lys63-linked Ubiquitination of RIG-I Promotes Cytokine Eruption in Early Influenza B Virus Infection.[/h] Jiang J[SUP]1[/SUP], Li J[SUP]2[/SUP], Fan W[SUP]3[/SUP], Zheng W[SUP]3[/SUP], Yu M[SUP]3[/SUP], Chen C[SUP]3[/SUP], Sun L[SUP]3[/SUP], Bi Y[SUP]3[/SUP], Ding C[SUP]4[/SUP], Gao GF[SUP]5[/SUP], Liu W[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza A and B virus infections both cause a host innate immunity response. Here, we report that the robust production of type I and III interferons (IFNs), IFN-stimulated genes, and pre-inflammatory factors can be induced by influenza B virus infection rather than influenza A virus in alveolar epithelial cells (A549) during early infection. This response is mainly dependent on the RIG-I-mediated signaling pathway. The infection by influenza B virus promotes intense Lys63-linked ubiquitination of RIG-I, resulting in cytokine eruption. It is known that the influenza A virus NS1 protein (NS1-A) interacts with RIG-I and TRIM25 to suppress the activation of RIG-I-mediated signaling. However, the present results indicate that the influenza B virus NS1 protein (NS1-B) is unable to interact with RIG-I but engages in the formation of a RIG-I/TRIM25/NS1-B ternary complex. Furthermore, we demonstrate that the N-terminal RNA-binding domain (RBD) of NS1-B is responsible for interaction with TRIM25, and this interaction blocks the inhibitory effect on RIG-I ubiquitination from the NS1-B C-terminus. Our findings reveal a novel mechanism for the host cytokine response to influenza B virus infection through regulatory interplay between host and viral proteins.
[h=4]IMPORTANCE:[/h] Influenza B virus generally causes local mild epidemics but is occasionally lethal to individuals. Existing studies describe the broad characteristics of influenza B virus epidemiology and pathology. However, to develop better prevention and treatments for the disease, determining the concrete molecular mechanisms of pathogenesis becomes pivotal to understand how the host reacts to the challenge of influenza B virus. Thus, we aimed to characterize the host innate immune response against influenza B virus infection. Here, we show that vigorous Lys63-linked ubiquitination of RIG-I and cytokine eruption dependent on RIG-I-mediated signal transduction are induced by virus infection. Additionally, TRIM25 positively regulates RIG-I-mediated signaling by ablating the inhibitory function of NS1-B on RIG-I ubiquitination.
Copyright ? 2016, American Society for Microbiology. All Rights Reserved.
PMID: 27122586 [PubMed - as supplied by publisher]
[h=1]Robust Lys63-linked Ubiquitination of RIG-I Promotes Cytokine Eruption in Early Influenza B Virus Infection.[/h] Jiang J[SUP]1[/SUP], Li J[SUP]2[/SUP], Fan W[SUP]3[/SUP], Zheng W[SUP]3[/SUP], Yu M[SUP]3[/SUP], Chen C[SUP]3[/SUP], Sun L[SUP]3[/SUP], Bi Y[SUP]3[/SUP], Ding C[SUP]4[/SUP], Gao GF[SUP]5[/SUP], Liu W[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza A and B virus infections both cause a host innate immunity response. Here, we report that the robust production of type I and III interferons (IFNs), IFN-stimulated genes, and pre-inflammatory factors can be induced by influenza B virus infection rather than influenza A virus in alveolar epithelial cells (A549) during early infection. This response is mainly dependent on the RIG-I-mediated signaling pathway. The infection by influenza B virus promotes intense Lys63-linked ubiquitination of RIG-I, resulting in cytokine eruption. It is known that the influenza A virus NS1 protein (NS1-A) interacts with RIG-I and TRIM25 to suppress the activation of RIG-I-mediated signaling. However, the present results indicate that the influenza B virus NS1 protein (NS1-B) is unable to interact with RIG-I but engages in the formation of a RIG-I/TRIM25/NS1-B ternary complex. Furthermore, we demonstrate that the N-terminal RNA-binding domain (RBD) of NS1-B is responsible for interaction with TRIM25, and this interaction blocks the inhibitory effect on RIG-I ubiquitination from the NS1-B C-terminus. Our findings reveal a novel mechanism for the host cytokine response to influenza B virus infection through regulatory interplay between host and viral proteins.
[h=4]IMPORTANCE:[/h] Influenza B virus generally causes local mild epidemics but is occasionally lethal to individuals. Existing studies describe the broad characteristics of influenza B virus epidemiology and pathology. However, to develop better prevention and treatments for the disease, determining the concrete molecular mechanisms of pathogenesis becomes pivotal to understand how the host reacts to the challenge of influenza B virus. Thus, we aimed to characterize the host innate immune response against influenza B virus infection. Here, we show that vigorous Lys63-linked ubiquitination of RIG-I and cytokine eruption dependent on RIG-I-mediated signal transduction are induced by virus infection. Additionally, TRIM25 positively regulates RIG-I-mediated signaling by ablating the inhibitory function of NS1-B on RIG-I ubiquitination.
Copyright ? 2016, American Society for Microbiology. All Rights Reserved.
PMID: 27122586 [PubMed - as supplied by publisher]