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The cytosolic DNA sensor cGAS recognizes viral DNA and synthesizes the second messenger cGAMP upon viral infection. cGAMP binds to the adaptor protein MITA/STING to activate downstream signaling events, leading to induction of type I interferons (IFNs) and antiviral effector genes. Here we identify the human cytomegalovirus (HCMV) protein UL31 as an inhibitor of cGAS. UL31 interacts directly with cGAS and disassociates DNA from cGAS, thus inhibiting cGAS enzymatic functions and reducing cGAMP production. UL31 overexpression markedly reduces antiviral responses stimulated by cytosolic DNA, while knockdown or knockout of UL31 heightens HCMV-triggered induction of type I IFNs and downstream antiviral genes. Moreover, wild-type HCMV replicates more efficiently than UL31-deficient HCMV, a phenotype that is reversed in cGAS null cells. These results highlight the importance of cGAS in the host response to HCMV as well as an important viral strategy to evade this innate immune sensor.
Pubmed ID: 29937271 RIS Download
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Software for aligning sequencing reads against large reference genome. Consists of three algorithms: BWA-backtrack, BWA-SW and BWA-MEM. First for sequence reads up to 100bp, and other two for longer sequences ranged from 70bp to 1Mbp.
View all literature mentionsA generic alignment format for storing read alignments against reference sequences, supporting short and long reads (up to 128 Mbp) produced by different sequencing platforms.
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