@article{132856,
  keywords = {Humans, Cell Line, Proteome, Protein Interaction Maps, Herpesvirus 1, Human, Apoptosis, Herpes Simplex, Interferons, Immunity, Innate, Cytokines, Nucleotidyltransferases},
  author = {Krystal Lum and Bokai Song and Joel Federspiel and Benjamin Diner and Timothy Howard and Ileana Cristea},
  title = {Interactome and Proteome Dynamics Uncover Immune Modulatory Associations of the Pathogen Sensing Factor cGAS},
  abstract = {<p>Viral DNA sensing is an essential component of the mammalian innate immune response. Upon binding viral DNA, the cyclic-GMP-AMP synthase (cGAS) catalyzes the production of cyclic dinucleotides to induce type I interferons. However, little is known about how cGAS is homeostatically maintained or\&nbsp;regulated upon infection. Here, we define cytoplasmic cGAS interactions with cellular and viral proteins upon herpes simplex virus type 1 (HSV-1) infection in primary human fibroblasts. We compare several HSV-1 strains (wild-type, d109, d106) that induce cytokine responses and apoptosis and place cGAS interactions in the context of temporal proteome alterations using isobaric-labeling mass spectrometry. Follow-up analyses establish a functional interaction between cGAS and 2{\textquoteright}-5{\textquoteright}-oligoadenylate synthase-like protein OASL. The OAS-like domain interacts with the cGAS Mab21 domain, while the OASL ubiquitin-like domain further inhibits cGAS-mediated interferon response. Our findings explain how cGAS may be inactively maintained in cellular homeostasis, with OASL functioning as a negative feedback loop for cytokine induction.</p>
},
  year = {2018},
  journal = {Cell Syst},
  volume = {7},
  pages = {627-642.e6},
  month = {12/2018},
  issn = {2405-4712},
  doi = {10.1016/j.cels.2018.10.010},
  language = {eng},
}