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

Jun-Kyu Lee; Jung-Eun Kim; Bang Ju Park; Yoon-Jae Song

doi:10.1007/s12275-020-9577-6

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Human cytomegalovirus IE86 protein aa 136–289 mediates STING degradation and blocks the cGAS-STING pathway: Jun-Kyu Lee ^1†, Jung-Eun Kim ^1,2†, Bang Ju Park ³, Yoon-Jae Song ¹; Journal of Microbiology 2020;58(1):54-60.
DOI: https://doi.org/10.1007/s12275-020-9577-6
Published online: January 2, 2020

¹Department of Life Science, Gachon University, Seongnam 13120, Republic of Korea, ²Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada, ³Department of Electronic Engineering, Gachon University, Seongnam 13120, Republic of Korea¹Department of Life Science, Gachon University, Seongnam 13120, Republic of Korea, ²Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada, ³Department of Electronic Engineering, Gachon University, Seongnam 13120, Republic of Korea

Corresponding author: Yoon-Jae Song , Tel: +82-31-750-8731,

Received: 3 December 2019 • Revised: 11 December 2019 • Accepted: 11 December 2019

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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 measurement 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.

Keywords: HCMV;IE86;STING;type I IFN

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

J. Microbiol. 2020;58(1):54-60. Published online January 2, 2020

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

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