Oligoadenylate-Synthetase-Family Protein OASL Inhibits Activity of the DNA Sensor cGAS during DNA Virus Infection to Limit Interferon Production
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2019
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| author | Ghosh, Arundhati Shao, Lulu Sampath, Padmavathi Zhao, Baoyu Patel, Nidhi V. Zhu, Jianzhong Behl, Bharat Parise, Robert A. Beumer, Jan H. O'Sullivan, Roderick J. DeLuca, Neal A. Thorne, Stephen H. Rathinam, Vijay A. K. Li, Pingwei Sarkar, Saumendra N. |
| author_facet | Ghosh, Arundhati Shao, Lulu Sampath, Padmavathi Zhao, Baoyu Patel, Nidhi V. Zhu, Jianzhong Behl, Bharat Parise, Robert A. Beumer, Jan H. O'Sullivan, Roderick J. DeLuca, Neal A. Thorne, Stephen H. Rathinam, Vijay A. K. Li, Pingwei Sarkar, Saumendra N. |
| contents | (Uploaded by Plazi for the Bat Literature Project) Interferon-inducible human oligoadenylate synthetase-like (OASL) and its mouse ortholog, Oasl2, enhance RNA-sensor RIG-I-mediated type I interferon (IFN) induction and inhibit RNA virus replication. Here, we show that OASL and Oasl2 have the opposite effect in the context of DNA virus infection. In Oasl2−/− mice and OASL-deficient human cells, DNA viruses such as vaccinia, herpes simplex, and adenovirus induced increased IFN production, which resulted in reduced virus replication and pathology. Correspondingly, ectopic expression of OASL in human cells inhibited IFN induction through the cGAS-STING DNA-sensing pathway. cGAS was necessary for the reduced DNA virus replication observed in OASL-deficient cells. OASL directly and specifically bound to cGAS independently of double-stranded DNA, resulting in a non-competitive inhibition of the second messenger cyclic GMP-AMP production. Our findings define distinct mechanisms by which OASL differentially regulates host IFN responses during RNA and DNA virus infection and identify OASL as a negative-feedback regulator of cGAS. |
| format | Recurso digital |
| id | zenodo_https___doi_org_10_5281_zenodo_13534104 |
| institution | Zenodo |
| language | |
| publishDate | 2019 |
| publisher | Zenodo |
| record_format | zenodo |
| spellingShingle | Oligoadenylate-Synthetase-Family Protein OASL Inhibits Activity of the DNA Sensor cGAS during DNA Virus Infection to Limit Interferon Production Ghosh, Arundhati Shao, Lulu Sampath, Padmavathi Zhao, Baoyu Patel, Nidhi V. Zhu, Jianzhong Behl, Bharat Parise, Robert A. Beumer, Jan H. O'Sullivan, Roderick J. DeLuca, Neal A. Thorne, Stephen H. Rathinam, Vijay A. K. Li, Pingwei Sarkar, Saumendra N. DNA virus IFN OASL cGAMP cGAS transcriptional signalling Biodiversity Mammalia Chiroptera Chordata Animalia bats bat (Uploaded by Plazi for the Bat Literature Project) Interferon-inducible human oligoadenylate synthetase-like (OASL) and its mouse ortholog, Oasl2, enhance RNA-sensor RIG-I-mediated type I interferon (IFN) induction and inhibit RNA virus replication. Here, we show that OASL and Oasl2 have the opposite effect in the context of DNA virus infection. In Oasl2−/− mice and OASL-deficient human cells, DNA viruses such as vaccinia, herpes simplex, and adenovirus induced increased IFN production, which resulted in reduced virus replication and pathology. Correspondingly, ectopic expression of OASL in human cells inhibited IFN induction through the cGAS-STING DNA-sensing pathway. cGAS was necessary for the reduced DNA virus replication observed in OASL-deficient cells. OASL directly and specifically bound to cGAS independently of double-stranded DNA, resulting in a non-competitive inhibition of the second messenger cyclic GMP-AMP production. Our findings define distinct mechanisms by which OASL differentially regulates host IFN responses during RNA and DNA virus infection and identify OASL as a negative-feedback regulator of cGAS. |
| title | Oligoadenylate-Synthetase-Family Protein OASL Inhibits Activity of the DNA Sensor cGAS during DNA Virus Infection to Limit Interferon Production |
| topic | DNA virus IFN OASL cGAMP cGAS transcriptional signalling Biodiversity Mammalia Chiroptera Chordata Animalia bats bat |
| url | https://doi.org/10.5281/zenodo.13534104 |