HSV-1-MEDIATED MODULATION OF CYTOKINE GENE-EXPRESSION IN A PERMISSIVECELL-LINE - SELECTIVE UP-REGULATION

Pathological effects of herpes simplex virus (HSV) can result due to a combination of direct viropathic effects and immunological reactions to viral antigens. The immunological reactions are orchestrated by a v ariety of cytokines and chemokines released by the host cells. Therefo re, the cytokine gene expression in response to HSV-1 infection in a p ermissive murine cell line was investigated. The data demonstrate that HSV-1 induced a selective activation of IL-6 gene expression at the m RNA and protein levels, in the permissive cell line. The cell line use d was capable of expressing IL-1, IL-7, and IL-10 in addition to IL-6, upon lipopolysaccharide stimulation. UV or heat-inactivated viruses w ere unable to upregulate IL-6 expression. However, mutant HSV-1 strain s lacking fully functional ICP0, ICP4, ICP8, or ICP27 genes, thereby r endering them replication incompetent or impaired in in vitro cell gro wth (ICP0), enhanced IL-6 expression selectively. Considering the role of IL-6 in inflammation, immune response, and its known association w ith increased levels of MyD116 and GADD 34 mRNAs (genes involved in th e prevention of apoptotic death of cells), the present data may have r elevance to HSV-1-mediated diseases as well as to the prevalence of HS V-1 in the host. (C) 1996 Academic Press, Inc.