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Human cytomegalovirus IE86 protein aa 136–289 mediates STING degradation and blocks the cGAS-STING pathway

  • Virology
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Abstract

We previously reported that human cytomegalovirus (HCMV) 86 kDa immediate-early 2 gene product (IE86) promotes proteasome-dependent degradation of STING. In the present study, we determined the specific residues of IE86 responsible for STING degradation using a STING-firefly luciferase fusion protein expression system for quantitative meas-urement of STING protein levels. IE86 amino acids (aa) 136-289 were sufficient to promote STING degradation and further induced down-regulation of 2′3′-cyclic GMP-AMP (cGAMP)-mediated IFN-β promoter activation. Interestingly, transactivation domains (TAD) of the IE86 protein located at the N- and C-termini were required for down-regulation of Toll/interleukin-1 receptor (TIR) domain-containing adaptor-inducing interferon β (IFN-β) (TRIF)-mediated IFN-β-and p65/RelA-induced NF-κB-dependent promoter activation while amino acids (aa) 136-289 had no significant effects. Our collective data suggest that the IE86 protein utilizes the aa 136-289 region to promote STING degradation and inhibit the cGAS-STING pathway.

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Acknowledgments

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Tech-nology (NRF-2017R1D1A1B03032494). This work was also supported by the Gachon University research fund of 2018 (GCU-2018-0362).

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Life Science, Gachon University, Seongnam, 13120, Republic of Korea

    Jun-Kyu Lee, Jung-Eun Kim & Yoon-Jae Song

  2. Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, Toronto, Ontario, M5G 0A4, Canada

    Jung-Eun Kim

  3. Department of Electronic Engineering, Gachon University, Seongnam, 13120, Republic of Korea

    Bang Ju Park

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  1. Jun-Kyu Lee
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  2. Jung-Eun Kim
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Correspondence to Yoon-Jae Song.

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Lee, JK., Kim, JE., Park, B.J. et al. Human cytomegalovirus IE86 protein aa 136–289 mediates STING degradation and blocks the cGAS-STING pathway. J Microbiol. 58, 54–60 (2020). https://doi.org/10.1007/s12275-020-9577-6

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  • DOI: https://doi.org/10.1007/s12275-020-9577-6

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