Viral protease cleavage of inhibitor of kappaBalpha triggers host cell apoptosis.
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 kappaBalpha (IkappaBalpha). A proteolytic fragment of IkappaBalpha then forms a stable complex with NF-kappaB, translocates to the nucleus, and inhibits NF-kappaB transactivation, increasing apoptosis and decreasing viral replication. In contrast, cells with reduced IkappaBalpha expression are more susceptible to viral infection, with less apoptosis and more viral replication. IkappaBalpha 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.
Zaragoza
Carlos
C
Fundación Centro Nacional de Investigaciones Cardiovasculares, Melchor Fernandez Almagro 3, 28029 Madrid, Spain. czaragoza@cnic.es
Saura
Marta
M
Padalko
Elizaveta Y
EY
Lopez-Rivera
Ester
E
Lizarbe
Tania R
TR
Lamas
Santiago
S
Lowenstein
Charles J
CJ
D000086042:3C Viral Proteases; D017209:Apoptosis; D002467:Cell Nucleus / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004770:Enterovirus / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D021381:Protein Transport; D014764:Viral Proteins / Q000378:metabolism*
D016328:NF-kappa B; D010446:Peptide Fragments; D014764:Viral Proteins; D051550:I-kappa B Kinase; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases