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Rubicon: a facilitator of viral immune evasion

Cellular & Molecular Immunology volume 16, pages 770–771 (2019)Cite this article

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In a study published in cellular and molecular immunology, Wan et al. demonstrate a new mechanism of viral immune evasion.1 It was observed that Rubicon, the RUN domain Beclin-1-interacting and cysteine-rich domain-containing protein, is induced by viral infection and antagonizes interferon (IFN) production, thereby facilitating viral replication. This study not only demonstrates a direct link between Rubicon and NF-κB essential modulator (NEMO), but also demonstrates how the interaction between Rubicon and NEMO inhibits the production of type I interferon. This study shows a previously unrecognized function of Rubicon as an important negative regulator of the innate immune response.

Rubicon was initially identified as a component of the Class III PI3K complex and as a negative regulator of canonical autophagy and endosomal trafficking. However, Rubicon has attracted much attention because of its identification as a key modulator of the inflammatory response and viral replication.6 Classically, Rubicon is known to regulate both autophagy and phagocytosis. Recent studies have demonstrated the role of Rubicon in the innate immune response to viral infection. Rubicon differentially targets signaling complexes, depending on environmental stimuli, and may function to coordinate various immune responses against microbial infections.7 Upon viral infection, the expression of Rubicon is enhanced, and it then facilitates viral replication. Wan et al. observed that Rubicon expression is elevated in patients with chronic hepatitis B infections. They also measured Rubicon mRNA and protein levels in HepG2 human hepatoma cells and in HepG2.2.15 cells that contain an integrated HBV genome and stably express HBV. Wan et al. found that HBV infection induced Rubicon expression. Next, the function of Rubicon during HBV infection was explored. They assessed HBV replication by measuring viral protein expression and DNA copy number in Rubicon-overexpressing and knockdown Huh7 cells. The results suggested that Rubicon enhances HBV replication.1 Moreover, a study demonstrated that Rubicon plays a positive role in HCV replication, as the suppression of its expression reduced HCV replication and its overexpression enhanced HCV replication.8 Recombinant Rubicon adenoviruses were used in an another study. Rubicon-expressing mice and Rubicon-depleted mice had approximately 100-fold higher and 100-fold lower viral loads, respectively, in their lungs compared to mice infected with Ad vector. Therefore, host defenses against viral infection are substantially affected by levels of Rubicon expression.7 Similar experiments were conducted with enterovirus 71, influenza A virus, and vesicular stomatitis virus; it was found that EV71, IAV, and VSV induced Rubicon expression, and Rubicon promoted their replication and production.1

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Authors and Affiliations

  1. State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, 430072, Wuhan, China

    Peining Fang, Haisheng Yu, Mengqi Li, Rui He, Ying Zhu & Shi Liu

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  1. Peining Fang
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Correspondence to Shi Liu.

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Fang, P., Yu, H., Li, M. et al. Rubicon: a facilitator of viral immune evasion. Cell Mol Immunol 16, 770–771 (2019). https://doi.org/10.1038/s41423-019-0248-7

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