title: Suppressor of Cytokine Signaling 3 Expression Induced by Varicella-Zoster Virus Infection Results in the Modulation of Virus Replication.
abstract: Varicella-zoster virus (VZV) is an important viral pathogen that is responsible for causing varicella (chickenpox) and herpes zoster (shingles). VZV has been shown to suppress early anti-viral innate immune responses, but the exact mechanisms are not yet well understood. Here we demonstrate that host control of VZV is impaired by the expression of suppressor of cytokine signaling (SOCS)3. We used three different cell types to characterize VZV-induced anti-viral and inflammatory responses. Infection of human fibroblasts (MRC-5) and human macrophages (THP-1) with VZV triggered upregulation of anti-viral responsive gene expression (IFN-α, IFN-β) in the early phases of infection, followed by the waning of these IFNs in the late phases of infection. Conversely, VZV infection in keratinocytes (HaCaT) resulted in a persistent increase in type I IFN gene expression. Interestingly, increase in SOCS1 and 3 expressions coincided with a reduction in phosphorylation of the signal transducer and activator of transcription protein 3 (STAT3) in VZV-infected MRC-5 cells. Furthermore, VZV infection increased the production of pro-inflammatory cytokines, including interleukin (IL)-6, -8, and IFN-γ-inducible protein 10 (IP-10). Knockdown of SOCS3 inhibited viral replication and enhanced secretion levels of IL-6, whereas overexpression of SOCS3 did not affect viral replication efficiency and host response. In conclusion, our data suggest that VZV infection induces SOCS3 expression, resulting in modulation of type I IFN signaling and viral replication.
authors.affiliation: BK21 Plus Graduate Program Biomedical Sciences, College of Medicine, Korea University, Seoul, Korea.|Asia-Pacific Alliance for the Control of Influenza, College of Medicine, Korea University, Seoul, Korea.
authors.forename: E-J
authors.initials: EJ
authors.lastname: Choi
authors.affiliation: Department of Microbiology, Chungbuk National University, Cheongju, Korea.
authors.forename: C-H
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, Korea.|Department of Microbiology, College of Medicine, Korea University, Seoul, Korea.
authors.forename: O S
authors.initials: OS
authors.lastname: Shin
mesh_terms: D002460:Cell Line; D002644:Chickenpox / Q000276:immunology / Q000821:virology; D002648:Child; D005260:Female; D005347:Fibroblasts / Q000276:immunology / Q000821:virology; D055785:Gene Knockdown Techniques; D006562:Herpes Zoster / Q000276:immunology / Q000821:virology*; D014645:Herpesvirus 3, Human / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis / Q000276:immunology*; D016899:Interferon-beta / Q000096:biosynthesis / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology / Q000821:virology; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis* / Q000235:genetics; D014779:Virus Replication / Q000502:physiology*
chemical_list: C508606:CXCL8 protein, human; C508600:IL6 protein, human; D016898:Interferon-alpha; D015850:Interleukin-6; D016209:Interleukin-8; C106644:SOCS3 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D016899:Interferon-beta; D007371:Interferon-gamma