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KMID : 0880220200580010054
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Journal of Microbiology
2020 Volume.58 No. 1 p.54 ~ p.60
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Human cytomegalovirus IE86 protein aa 136?289 mediates STING degradation and blocks the cGAS-STING pathway
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Lee Jun-Kyu
Kim Jung-Eun
Park Bang-Ju
Song Yoon-Jae
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Abstract
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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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KEYWORD
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HCMV, IE86, STING, type I IFN
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