OASL1 deficiency promotes antiviral protection against genital herpes simplex virus type 2 infection by enhancing type i interferon production

Ji Eun Oh, Myeong Sup Lee, Young Joon Kim, Heung Kyu Lee

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15 Citations (Scopus)

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, Ly6Chigh 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.

Original languageEnglish
Article number19089
JournalScientific reports
Volume6
DOIs
Publication statusPublished - 2016 Jan 11

Bibliographical note

Funding Information:
The authors would like to thank the members of the Laboratory of Host Defenses for helpful advice on experiments and data discussions. The authors also thank SJ Kang for MOB mice. This work was supported by the National Research Foundation (NRF-2015R1A4A1042416, NRF-2014M3A9A5044964, NRF-2012R1A1A2046001, and NRF-2012M3A9B4028274), the Converging Research Center Program (2014M3C1A8048778), and the KAIST Future Systems Healthcare project funded by the Ministry of Science, ICT, and Future Planning of Korea. This study was also supported by the Korean Health Technology R & D Project (A100920), which is funded by the Ministry of Health & Welfare, Republic of Korea. YJ Kim was supported by the Bio & Medical Technology Development Program of the National Research Foundation funded by the Ministry of Science, ICT & Future Planning (NRF-2012M3A9B4028272).

All Science Journal Classification (ASJC) codes

  • General

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