Viral protease cleavage of inhibitor of κBα triggers host cell apoptosis

Carlos Zaragoza, Marta Saura, Elizaveta Y. Padalko, Ester Lopez-Rivera, Tania R. Lizarbe, Santiago Lamas, Charles J. Lowenstein

Research output: Contribution to journalArticlepeer-review

49 Scopus citations


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 3Cpro 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 IκBα 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.

Original languageEnglish (US)
Pages (from-to)19051-19056
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number50
StatePublished - Dec 12 2006


  • Coxsackievirus
  • Nitric oxide
  • Picornavirus

ASJC Scopus subject areas

  • General


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