Inhibitor of NFκB Alpha is a Host Sensor of Coxsackievirus Infection

Marta Saura, Tania R. Lizarbe, Concepcion Rama-Pacheco, Charles J. Lowenstein and Carlos Zaragoza

volume 6 | issue 5

1 March 2007
Pages: 503 - 506

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Apoptosis is a host response to viral infection: programmed cell death can limit viral replication. Therefore, the knowledge of pathways by which cells detect viral infection and activate apoptosis may be of considerable interest when developing strategies against viral pathogens. We have shown that cells activate apoptosis in response to Coxsackievirus B3 (CVB3) infection. In an effort to discover how cells detect viral infections, we found that the viral protease 3Cpro cleaves IκBα. Truncated IκBα forms a stable complex with NFκB, translocates to the nucleus, and inhibits NF-κB trans-activation, increasing apoptosis and decreasing viral replication. In contrast, cells in which IκBα expression is reduced are more susceptible to viral infection, showing 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.

Authors

Marta Saura

Departamento de Fisiologia, Facultad de Medicina, Universidad de Alcala; Alcala de Henares, Spain

Tania R. Lizarbe

2Centro Nacional de Investigaciones Cardiovasculares, Instituto de Salud Carlos III; Madrid, Spain

Concepcion Rama-Pacheco

Centro Nacional de Investigaciones Cardiovasculares, Instituto de Salud Carlos III; Madrid, Spain

Charles J. Lowenstein

Division of Cardiology, Department of Medicine, The Johns Hopkins University School of Medicine; Baltimore, Maryland USA

Carlos Zaragoza