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J Biol Chem. 2019 Aug 2. pii: jbc.RA119.007917. doi: 10.1074/jbc.RA119.007917. [Epub ahead of print]

The small GTPase RAB1B promotes antiviral innate immunity by interacting with TNF receptor-associated factor 3 (TRAF3).

Author information

1
Duke University Medical Center.
2
Duke University Medical Center, United States.

Abstract

Innate immune detection of viral nucleic acids during viral infection activates a signaling cascade that induces type I and type III interferons (IFNs), as well as other cytokines, to generate an antiviral response. This signaling is initiated by pattern recognition receptors, such as the RNA helicase retinoic acid-inducible gene I (RIG-I), that sense viral RNA. These sensors then interact with the adaptor protein mitochondrial antiviral signaling protein (MAVS), which recruits additional signaling proteins, including TNF receptor-associated factor 3 (TRAF3) and TANK-binding kinase 1 (TBK1), to form a signaling complex that activates IFN regulatory factor 3 (IRF3) for transcriptional induction of type I IFNs. Here, using several immunological and biochemical approaches in multiple human cell types, we show that the GTPase-trafficking protein RAB1B up-regulates RIG-I pathway signaling and thereby promotes IFN-β induction and the antiviral response. We observed that RAB1B over-expression increases RIG-I-mediated signaling to IFN-β and that RAB1B deletion reduces signaling of this pathway. Additionally, loss of RAB1B dampened the antiviral response, indicated by enhanced Zika virus infection of cells depleted of RAB1B. Importantly, we identified the mechanism of RAB1B action in the antiviral response, finding that it forms a protein complex with TRAF3 to facilitate the interaction of TRAF3 with MAVS. We conclude that RAB1B regulates TRAF3 and promotes the formation of innate immune signaling complexes in response to nucleic acid sensing during RNA virus infection.

KEYWORDS:

MAVS; RAB1B; RNA virus; TRAF3; antiviral agent; flavivirus; innate immunity; interferon

PMID:
31375559
DOI:
10.1074/jbc.RA119.007917
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