tetano
Editor, Senior Moderator
Cell Rep. 2016 Mar 2. pii: S2211-1247(16)30134-6. doi: 10.1016/j.celrep.2016.02.031. [Epub ahead of print]
[h=1]CARMA3 Is a Host Factor Regulating the Balance of Inflammatory and Antiviral Responses against Viral Infection.[/h] Jiang C[SUP]1[/SUP], Zhou Z[SUP]2[/SUP], Quan Y[SUP]1[/SUP], Zhang S[SUP]3[/SUP], Wang T[SUP]1[/SUP], Zhao X[SUP]3[/SUP], Morrison C[SUP]4[/SUP], Heise MT[SUP]4[/SUP], He W[SUP]5[/SUP], Miller MS[SUP]6[/SUP], Lin X[SUP]7[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Host response to RNA virus infection is sensed by RNA sensors such as RIG-I, which induces MAVS-mediated NF-κB and IRF3 activation to promote inflammatory and antiviral responses, respectively. Here, we have found that CARMA3, a scaffold protein previously shown to mediate NF-κB activation induced by GPCR and EGFR, positively regulates MAVS-induced NF-κB activation. However, our data suggest that CARMA3 sequesters MAVS from forming high-molecular-weight aggregates, thereby suppressing TBK1/IRF3 activation. Interestingly, following NF-κB activation upon virus infection, CARMA3 is targeted for proteasome-dependent degradation, which releases MAVS to activate IRF3. When challenged with vesicular stomatitis virus or influenza A virus, CARMA3-deficient mice showed reduced disease symptoms compared to those of wild-type mice as a result of less inflammation and a stronger ability to clear infected virus. Altogether, our results reveal the role of CARMA3 in regulating the balance of host antiviral and pro-inflammatory responses against RNA virus infection.
Copyright ? 2016 The Authors. Published by Elsevier Inc. All rights reserved.
[h=4]KEYWORDS:[/h] CARD10; CARMA3; IRF3; NF-κB; viral infection
PMID: 26947079 [PubMed - as supplied by publisher]
[h=1]CARMA3 Is a Host Factor Regulating the Balance of Inflammatory and Antiviral Responses against Viral Infection.[/h] Jiang C[SUP]1[/SUP], Zhou Z[SUP]2[/SUP], Quan Y[SUP]1[/SUP], Zhang S[SUP]3[/SUP], Wang T[SUP]1[/SUP], Zhao X[SUP]3[/SUP], Morrison C[SUP]4[/SUP], Heise MT[SUP]4[/SUP], He W[SUP]5[/SUP], Miller MS[SUP]6[/SUP], Lin X[SUP]7[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Host response to RNA virus infection is sensed by RNA sensors such as RIG-I, which induces MAVS-mediated NF-κB and IRF3 activation to promote inflammatory and antiviral responses, respectively. Here, we have found that CARMA3, a scaffold protein previously shown to mediate NF-κB activation induced by GPCR and EGFR, positively regulates MAVS-induced NF-κB activation. However, our data suggest that CARMA3 sequesters MAVS from forming high-molecular-weight aggregates, thereby suppressing TBK1/IRF3 activation. Interestingly, following NF-κB activation upon virus infection, CARMA3 is targeted for proteasome-dependent degradation, which releases MAVS to activate IRF3. When challenged with vesicular stomatitis virus or influenza A virus, CARMA3-deficient mice showed reduced disease symptoms compared to those of wild-type mice as a result of less inflammation and a stronger ability to clear infected virus. Altogether, our results reveal the role of CARMA3 in regulating the balance of host antiviral and pro-inflammatory responses against RNA virus infection.
Copyright ? 2016 The Authors. Published by Elsevier Inc. All rights reserved.
[h=4]KEYWORDS:[/h] CARD10; CARMA3; IRF3; NF-κB; viral infection
PMID: 26947079 [PubMed - as supplied by publisher]