Søby, Stine5; Laursen, Rune R2; Østergaard, Lars Jørgen6; Melchjorsen, Jesper7
1 Department of Molecular Biology and Genetics, Science and Technology, Aarhus University2 Department of Molecular Biology, Faculty of Science, Aarhus University, Aarhus University3 Department of Clinical Medicine - Department of Infectious Diseases, Department of Clinical Medicine, Health, Aarhus University4 Department of Clinical Medicine, Health, Aarhus University5 Department of Molecular Biology and Genetics, Science and Technology, Aarhus University6 Department of Clinical Medicine - Department of Infectious Diseases, Department of Clinical Medicine, Health, Aarhus University7 Department of Clinical Medicine, Health, Aarhus University
ABSTRACT: BACKGROUND: Innate recognition is essential in the antiviral response against infection by herpes simplex virus (HSV). Chemokines are important for control of HSV via recruitment of natural killer cells, T lymphocytes, and antigen-presenting cells. We previously found that early HSV-1-mediated chemokine responses are not dependent on TLR2 and TLR9 in human macrophages. Here, we investigated the role of the recently identified innate IFN-inducible DNA receptor IFI16 during HSV-1 infection in human macrophages. METHODS: Peripheral blood mononuclear cells were purified from buffy coats and monocytes were differentiated to macrophages. Macrophages infected with HSV-1 were analyzed using siRNA-mediated knock-down of IFI16 by real-time PCR, ELISA, and Western blotting. RESULTS: We determined that both CXCL10 and CCL3 are induced independent of HSV-1 replication. IFI16 mediates CCL3 mRNA accumulation during early HSV-1 infection. In contrast, CXCL10 was induced independently of IFI16. CONCLUSIONS: Our data provide the first evidence of HSV-1-induced innate immune responses via IFI16 in human primary macrophages. In addition, the data suggest that at least one additional unidentified receptor or innate sensing mechanism is involved in recognizing HSV-1 prior to viral replication.