title: OASL1 deficiency promotes antiviral protection against genital herpes simplex virus type 2 infection by enhancing type I interferon production.
abstract: Type I interferon (IFN) interferes with virus replication, promotes antiviral responses, and controls innate and adaptive immune responses to certain viruses. Recently, we reported that 2'-5' oligoadenylate synthetase-like 1 (OASL1) negatively regulates type I IFN production by inhibiting the translation of the type I IFN-regulating master transcription factor, IRF7. Notably, while OASL1-deficient mice induce robust production of type I IFN and are resistant to systemic viral infection, the effects of OASL1 during localized viral infection has not been studied. To this end, we investigated the role of OASL1 during mucosal HSV-2 infection of the genital tract. Oasl1(-/-) mice exhibited better survival rates than wild type (WT) mice following intravaginal HSV-2 infection, and suppressed virus replication more efficiently despite comparable recruitment of effector immune cells. Moreover, Ly6C(high) monocytes, and not pDCs or other cell types, displayed enhanced production of type I IFNs in Oasl1(-/-) mice in response to HSV-2 infection. Furthermore, cytotoxic T cell responses including IFN-γ production were accelerated in Oasl1(-/-) mice after mucosal HSV-2 infection. Collectively, these results demonstrate that OASL1 deficiency promotes antiviral immunity against local mucosal viral infection and suggest that OASL1 could be a therapeutic target for treatment of HSV-2 infection of the genital mucosa.
authors.affiliation: Laboratory of Host Defenses, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Oh
authors.affiliation: Department of Biomedical Sciences, College of Medicine, University of Ulsan, Seoul, 05505, Republic of Korea.
authors.forename: Myeong Sup
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, College of Life Science and Technology, Yonsei University, Seoul, 03722, Republic of Korea.|Department of Integrated Omics for Biomedical Science Graduate School, Yonsei University, Seoul, 03722, Republic of Korea.
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Laboratory of Host Defenses, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.
authors.forename: Heung Kyu
authors.initials: HK
authors.lastname: Lee
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000172:deficiency* / Q000378:metabolism; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D000950:Antigens, Ly / Q000378:metabolism; D000998:Antiviral Agents / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000378:metabolism; D002465:Cell Movement; D045142:Cross-Priming / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D006410:Hematopoiesis; D006558:Herpes Genitalis / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D018258:Herpesvirus 2, Human / Q000276:immunology*; D007113:Immunity, Innate; D007249:Inflammation / Q000473:pathology; D007370:Interferon Type I / Q000096:biosynthesis*; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000378:metabolism; D009092:Mucous Membrane / Q000473:pathology / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000950:Antigens, Ly; D000998:Antiviral Agents; D016207:Cytokines; D007370:Interferon Type I; C494192:Ly-6C antigen, mouse; C475083:Oasl1 protein, mouse; D015088:2',5'-Oligoadenylate Synthetase