Induction of interferon-λ contributes to TLR3 and RIG-I activation-mediated inhibition of herpes simplex virus type 2 replication in human cervical epithelial cells

摘要: Study hypothesis Is it possible to immunologically activate human cervical epithelial cells produce antiviral factors that inhibit herpes simplex virus type 2 (HSV-2) replication? finding Our results indicate possess a functional TLR3/RIG-I signaling system, the activation of which can mount an Interferon-λ (IFN-λ)-mediated anti-HSV-2 response. What is known already There limited information about role in genital innate immunity against HSV-2 infection. design, samples/materials, methods We examined expression toll-like receptors (TLRs) and retinoic acid-inducible I (RIG-I) End1/E6E7 by real-time PCR. The IFN-λ induced TLR3 RIG-I was also PCR ELISA. infection evaluated detection gD expression. antibody IL-10Rβ used determine whether contributes mediated inhibition. Expression interferon regulatory factor 3 (IRF3), IRF7, IFN-stimulated gene 56 (ISG56), 2'-5'-oligoadenylate synthetase (OAS-1) myxovirus resistance A (MxA) were determined western blot. transfected with shRNA knockdown IRF3, IRF7 or Student's t-test post Newman-Keuls test analyze stabilized differences immunological parameters above between TLR3/RIG-I-activated control cells. Main chance Human expressed RIG-I, could be activated poly I:C 5'ppp double-strand RNAs (5'ppp dsRNA), resulting induction endogenous lambda (IFN-λ). contributed TLR3/RIG-I-mediated inhibition replication cells, as IL-10Rβ, receptor subunit, compromise HSV-2. Further studies showed dsRNA genes (ISGs), ISG56, (MxA), key elements IFN pathway. In addition, we observed topical treatment mucosa protect mice from Limitations, reasons for caution Future prospective primary suitable animal models are needed order confirm these outcomes. Wider implications findings provide direct compelling evidence there intracellular regulation may have protection viral infections. Large scale data Not applicable. funding competing interests This work supported National Natural Science Foundation China (81301428 L.Z. 81271334 W.-Z.H.), Fundamental Research Funds Central Universities (2042015kf0188 L.Z.), Postdoctoral (2013M531745 Development Program ('973', 2012CB518900 W.-Z.H.) Ministry Technology People's Republic China, grants (DA12815 DA022177 Institute on Drug Abuse (NIDA) open project Hubei Key Laboratory Wudang Local Chinese Medicine (WDCM005 M.S.). authors declare no financial interests.