Activation of IκB Kinase by Herpes Simplex Virus Type 1

• Published in: The Journal of biological chemistry 2001-08, Vol.276 (31), p.28759
• Main Authors: Carla Amici, Giuseppe Belardo, Antonio Rossi, M. Gabriella Santoro
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M103408200

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