Zaragoza Carlos, Saura Marta, Padalko Elizaveta Y, Lopez-Rivera Ester, Lizarbe Tania R, Lamas Santiago, Lowenstein Charles J
Fundación Centro Nacional de Investigaciones Cardiovasculares, Melchor Fernandez Almagro 3, 28029 Madrid, Spain.
Proc Natl Acad Sci U S A. 2006 Dec 12;103(50):19051-6. doi: 10.1073/pnas.0606019103. Epub 2006 Nov 30.
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.
细胞凋亡是机体针对病毒感染的一种先天性免疫反应，可限制病毒复制。然而，细胞检测病毒感染并激活细胞凋亡的机制尚未完全明确。我们现在发现，在柯萨奇病毒感染期间，病毒蛋白酶3C（pro）可切割κB抑制蛋白α（IkappaBalpha）。IkappaBalpha的一个蛋白水解片段随后与核因子κB（NF-κB）形成稳定复合物，转位至细胞核，并抑制NF-κB的反式激活，从而增加细胞凋亡并减少病毒复制。相反，IkappaBalpha表达降低的细胞对病毒感染更敏感，细胞凋亡较少，病毒复制更多。因此，IkappaBalpha可作为病毒感染的一种感受器。病原体蛋白酶对宿主蛋白的切割是宿主识别和应对病毒感染的一种新机制。
