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Immune evasion

See no evil

Nature Reviews Microbiology volume 12, page 593 (2014)Cite this article

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This article has been updated

The RLR family includes RIG-I and melanoma differentiation-associated protein 5 (MDA5), which recognize viral double-stranded RNA structures. Following RNA recognition, RIG-I and MDA5 form complexes with the mitochondrial antiviral signalling protein (MAVS) via their caspase activation and recruitment domains (CARDs). These interactions trigger downstream signalling pathways that result in the production of antiviral type I interferons. RLR-induced signalling is regulated by the phosphatase PP1, which dephosphorylates specific residues in the CARDs of RIG-I and MDA5, enabling their interaction with MAVS. Notably, paramyxoviruses — the family that includes measles virus — have been shown to interfere with RLR-induced signalling pathways by targeting MDA5 via a non-structural viral protein, the V protein, although the precise mechanisms of this interaction are unknown. Now, Mesman et al. and Davis et al. show that measles virus targets PP1 to block the dephosphorylation of RIG-I and MDA5, which inhibits the production of type I interferon.

By carrying out co-immunoprecipitation (coIP) assays, Davis et al. found that measles virus V protein (MV-V) binds to PP1. Furthermore, the authors identified a conserved four-residue motif in the carboxy-terminal tail of MV-V that is responsible for PP1 binding. They constructed a recombinant virus strain that expressed a truncated version of MV-V lacking the C-terminal tail (VΔtail), which displayed reduced replication capacity following infection of lung epithelial cell lines, compared with wild-type virus. Analysis of VΔtail virus-infected cells at late time points following infection showed the presence of dephosphorylated MDA5. These data suggest that MV-V recruits PP1 away from MDA5, which prevents MDA5 activation by dephosphorylation.

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Change history

  • 04 August 2014

    In the original version of this highlight, retinoic-acid-inducible gene I (RIG-I) was incorrectly defined as retinoic acid-inducible protein 1 (RIG1). The online version of this article has been corrected. We apologize for any confusion caused.

References

  1. Davis, M. E. et al. Antagonism of the phosphatase PP1 by the measles virus V protein is required for innate immune escape of MDA5. Cell Host Microbe 16, 19–30 (2014)

    Article  CAS  Google Scholar 

  2. Mesman, A. W. et al. Measles virus supresses RIG-I-like receptor activation in dendritic cells via DC-SIGN-mediated inhibition of PP1 phosphatases. Cell Host Microbe 16, 31–42 (2014)

    Article  CAS  Google Scholar 

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Authors
  1. Cláudio Nunes-Alves
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Nunes-Alves, C. See no evil. Nat Rev Microbiol 12, 593 (2014). https://doi.org/10.1038/nrmicro3327

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