Activation of I kappa B kinase by herpes simplex virus type 1 - A novel target for anti-herpetic therapy

Herpes simplex viruses (HSV) are ubiquitous pathogens causing a variety of diseases ranging from mild illness to severe life-threatening infections. HSV utilize cellular signaling pathways and transcription factors to promote their replication. Here we report that HSV type 1 (HSV-1) induces persistent activation of transcription factor NF-kappaB, a critical regulator of genes involved in inflammation, by activating the I kappaB kinase (IKK) in the early phase of infection. Activated NF-kappaB enhances HSV-1 gene expression. HSV-1-induced NF-kappaB activation is dependent on viral early protein synthesis and is not blocked by the anti-herpetic drug acyclovir. IKK inhibition by the anti-inflammatory cyclopentenone prostaglandin A(1) blocks HSV-1 gene expression and reduces virus yield by more than 3000-fold. The results identify IKK as a potential target for anti-herpetic drugs and suggest that cyclopentenone prostaglandins or their derivatives could be used in the treatment of HSV infection.