Interleukin-27 Inhibits Herpes Simplex Virus Type 1 Infection by Activating STAT1 and 3, Interleukin-6, and Chemokines IP-10 and MIG.
Interleukin-27 (IL-27) inhibits the replication of many viruses, but the mechanism differs according to virus and cell type. In this study, we observed that IL-27 expression was upregulated in herpes simplex virus type 1 (HSV-1)-infected SJL/J mice, which led us to further investigate the role of IL-27 in HSV-1 infection using epithelial, glioma, and immunological cells as cell models. We showed that in all studied cell lines, the IL-27 messenger RNA (mRNA) level was upregulated due to the HSV-1 infection. When the cells were primed with IL-27 before the virus infection, the virus release was prevented, indicating an antiviral role of IL-27 in HSV-1 infection. Furthermore, we observed that IL-27 secretion to the culture medium was reduced in infected epithelial and immunological cells, but not in glioma cells. Not surprisingly, HSV-1 induced type I, II, and III interferons regardless of cell line, but IL-27 itself caused varying interferon responses dependent on cell type. However, common to all cell types was the IL-27-stimulated secretion of IL-6 and chemokines IP-10 and MIG. In addition, IL-27 stimulation activated STAT1 and STAT3 in HeLa and T98G cells, suggesting that IL-27 engages the STAT1/3 pathway, which then leads to the upregulation of IL-6, IP-10, and MIG.
1 Department of Virology, University of Turku , Turku, Finland .
Outi
O
Heikkilä
1 Department of Virology, University of Turku , Turku, Finland .
Michaela
M
Nygårdas
1 Department of Virology, University of Turku , Turku, Finland .|2 Drug Research Doctoral Programme, University of Turku , Turku, Finland .
Henrik
H
Paavilainen
1 Department of Virology, University of Turku , Turku, Finland .
Elina
E
Ryödi
1 Department of Virology, University of Turku , Turku, Finland .
Veijo
V
Hukkanen
D000818:Animals; D054357:Chemokine CXCL10 / Q000378:metabolism*; D054370:Chemokine CXCL9 / Q000378:metabolism*; D002522:Chlorocebus aethiops; D005260:Female; D006367:HeLa Cells; D006561:Herpes Simplex / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000235:genetics; D006801:Humans; D064094:Interleukin-27 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D014709:Vero Cells
C114753:CXCL10 protein, human; C080810:CXCL9 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D064094:Interleukin-27; D015850:Interleukin-6; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human
Interleukin 27; antiviral; chemokine; cytokine; herpes simplex virus; interferon