NEURONAL REACTIVATION OF HERPES-SIMPLEX VIRUS MAY INVOLVE INTERLEUKIN-6

Interleukin-6 (IL-6) is an inflammatory cytokine produced in many tiss ues, including the cornea and trigeminal ganglion. IL-6 acts by bindin g to its specific receptor, stimulating a cascade of signal proteins t hat induce the transcription factors NF-IL6 and STAT3. These IL-6-indu ced transcription factors change cellular gene transcription. Neutrali zation of IL-6 in vivo inhibits herpes simplex virus type 1 (HSV-1) oc ular reactivation in mice, There are IL-6 response elements, possible binding sites of the IL-6 induced transcription factors, within the HS V-1 genome, These IL-6 response elements are concentrated in the inver ted repeat regions of the genome, occurring in a non-random fashion in the promoters of the LAT and ICPO genes. Viral constructs containing deletions of IL-6 response elements in the LAT promoter region reactiv ate at a lower frequency compared with similar constructs lacking such deletions, HSV-1 may have evolved to exploit the relationship between a major inflammatory cytokine, IL-6, and conditions favorable for neu ronal reactivation and subsequent replication in the epithelium. Explo ring the role of IL-6, its receptor, and induced transcription factors in HSV-1 reactivation is a promising new avenue of research into the mechanism of HSV reactivation.