Abstract
The molluscum contagiosum virus (MCV) uses a variety of immune evasion strategies to antagonize host immune responses. Two MCV proteins, MC159 and MC160, contain tandem death effector domains (DEDs). They are reported to inhibit innate immune signaling events such as NF-κB and IRF3 activation, and apoptosis. The RxDL motif of MC159 is required for inhibition of both apoptosis and NF-κB activation. However, the role of the conserved RxDL motif in the MC160 DEDs remained unknown. To answer this question, we performed alanine mutations to neutralize the arginine and aspartate residues present in the MC160 RxDL in both DED1 and DED2. These mutations were further modeled against the structure of the MC159 protein. Surprisingly, the RxDL motif was not required for MC160′s ability to inhibit MAVS-induced IFNβ activation. Further, unlike previous results with the MC159 protein, mutations within the RxDL motif of MC160 had no effect on the ability of MC160 to dampen TNF-α-induced NF-κB activation. Molecular modeling predictions revealed no overall changes to the structure in the MC160 protein when the amino acids of both RxDL motifs were mutated to alanine (DED1 = R67A D69A; DED2 = R160A D162A). Taken together, our results demonstrate that the RxDL motifs present in the MC160 DEDs are not required for known functions of the viral protein.
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Acknowledgements
We would like to thank Joanna Shisler. This work was funded by Seton Hall University and the Seton Hall University Research Council. Structure coordinates of the homology model of MC160 are available upon request.
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MB, UKV, SW, CS, TTT, and DBN have made substantial contributions to work described herein.
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Beaury, M., Velagapudi, U.K., Weber, S. et al. The molluscum contagiosum virus death effector domain containing protein MC160 RxDL motifs are not required for its known viral immune evasion functions. Virus Genes 53, 522–531 (2017). https://doi.org/10.1007/s11262-017-1456-9
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DOI: https://doi.org/10.1007/s11262-017-1456-9