Human Cytomegalovirus UL138 Protein Inhibits the STING Pathway and Reduces Interferon Beta mRNA Accumulation during Lytic and Latent Infections.
Human Cytomegalovirus UL138 Protein Inhibits the STING Pathway and Reduces Interferon Beta mRNA Accumulation during Lytic and Latent Infections.
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DOI：
10.1128/mbio.02267-21
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发表时间：
2021-12-21
期刊：
影响因子：
6.4
通讯作者：
Kalejta RF
中科院分区：
文献类型：
--
作者：
Albright ER;Mickelson CK;Kalejta RF
cGAS/STING/TBK 1（环鸟嘌呤单磷酸-AMP合酶/干扰素基因刺激物/Tank结合激酶1）先天免疫途径在完全分化的细胞中的人巨细胞病毒（HCMV）生产性（裂解性）复制期间和在不完全分化的骨髓细胞中的潜伏期期间被激活。虽然多个溶细胞期HCMV蛋白中和沿着该途径的沿着步骤，但它们中没有一个在潜伏期期间表达。在这里，我们表明潜伏相关蛋白UL 138在转染和感染期间，在完全分化的细胞和不完全分化的骨髓细胞中，以及在功能丧失和功能恢复方法中抑制cGAS/STING/TBK 1先天免疫途径。UL 138抑制STING下游但干扰素调节因子3（IRF 3）磷酸化和NF-κB功能上游的途径，并减少裂解和潜伏感染期间干扰素β mRNA的积累。
The cGAS/STING/TBK1 (cyclic guanine monophosphate-AMP synthase/stimulator of interferon genes/Tank-binding kinase 1) innate immunity pathway is activated during human cytomegalovirus (HCMV) productive (lytic) replication in fully differentiated cells and during latency within incompletely differentiated myeloid cells. While multiple lytic-phase HCMV proteins neutralize steps along this pathway, none of them are expressed during latency. Here, we show that the latency-associated protein UL138 inhibits the cGAS/STING/TBK1 innate immunity pathway during transfections and infections, in fully differentiated cells and incompletely differentiated myeloid cells, and with loss of function and restoration of function approaches. UL138 inhibits the pathway downstream of STING but upstream of interferon regulatory factor 3 (IRF3) phosphorylation and NF-κB function and reduces the accumulation of interferon beta mRNA during both lytic and latent infections.