Viral Protease Cleavage of Inhibitor of κBα Triggers Host Cell Apoptosis

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 103; no. 50; pp. 19051 - 19056
• Main Authors: Zaragoza, Carlos, Saura, Marta, Padalko, Elizaveta Y., Lopez-Rivera, Ester, Lizarbe, Tania R., Lamas, Santiago, Lowenstein, Charles J.
• Format: Journal Article
• Language: English
• Published: National Academy of Sciences 12.12.2006; National Acad Sciences
• Subjects: Antibodies; Apoptosis; Biological Sciences; Cell nucleus; Cellular immunity; Coxsackievirus; HeLa cells; Infections; Oligonucleotides; Small interfering RNA; Transactivation; Viral infections
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0606019103

Apoptosis is an innate immune response to viral infection that limits viral replication. However, the mechanisms by which cells detect viral infection and activate apoptosis are not completely understood. We now show that during Coxsackievirus infection, the viral protease $3C^{pro}$ cleaves inhibitor of κBα (IκBα). A proteolytic fragment of IκBα then forms a stable complex with NF-κB, translocates to the nucleus, and inhibits NF-κB transactivation, increasing apoptosis and decreasing viral replication. In contrast, cells with reduced IKBa expression are more susceptible to viral infection, with less apoptosis and more viral replication. IκBα thus acts as a sensor of viral infection. Cleavage of host proteins by pathogen proteases is a novel mechanism by which the host recognizes and responds to viral infection.