TY - JOUR
T1 - Viral protease cleavage of inhibitor of κBα triggers host cell apoptosis
AU - Zaragoza, Carlos
AU - Saura, Marta
AU - Padalko, Elizaveta Y.
AU - Lopez-Rivera, Ester
AU - Lizarbe, Tania R.
AU - Lamas, Santiago
AU - Lowenstein, Charles J.
PY - 2006/12/12
Y1 - 2006/12/12
N2 - 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.
AB - 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.
KW - Coxsackievirus
KW - Nitric oxide
KW - Picornavirus
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U2 - 10.1073/pnas.0606019103
DO - 10.1073/pnas.0606019103
M3 - Article
C2 - 17138672
AN - SCOPUS:33947323399
SN - 0027-8424
VL - 103
SP - 19051
EP - 19056
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 50
ER -