prostaglandin-a1 and Laryngeal-Neoplasms

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-kappa B, a critical regulator of genes involved in inflammation, by activating the I kappa B kinase (IKK) in the early phase of infection. Activated NF-kappa B enhances HSV-1 gene expression. HSV-1-induced NF-kappa B 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.

Topics: Acyclovir; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antiviral Agents; Chlorocebus aethiops; Cycloheximide; Dactinomycin; Drug Design; Enzyme Activation; Enzyme Inhibitors; Gene Expression Regulation, Fungal; Herpesvirus 1, Human; Humans; I-kappa B Kinase; Kinetics; Laryngeal Neoplasms; Methionine; Neuroblastoma; NF-kappa B; Prostaglandins A; Protein Serine-Threonine Kinases; Recombinant Proteins; Transfection; Tumor Cells, Cultured; Vero Cells; Virus Replication