Coxsackievirus B3 activates nuclear factor kappa B transcription factor via a phosphatidylinositol‐3 kinase/protein kinase B‐dependent pathway to improve host cell viability

Summary Coxsackievirus B3 (CVB3) is the most common viral infectant of heart muscle. CVB3 directly injures cardiomyocytes. We have previously reported on a regulatory role for the phosphatidylinositol‐3 kinase (PI3K)/protein kinase B (Akt) pathway during CVB3 infection. Yet, the mechanism underlying this regulatory role has not been elucidated. The PI3K/Akt pathway is involved in various cellular processes and exerts its function through the activation of several downstream effectors. Among them, nuclear factor kappa B (NFκB) transcription factor is involved in inflammation, survival and apoptosis. In this study, we investigated the role of NFκB as a potential downstream mediator of signals through the PI3K/Akt cascade, in regulating CVB3‐induced cellular injury. We report that CVB3 infection induces the translocation of NFκB into the nucleus of infected cells. Inhibition of the PI3K/Akt pathway markedly decreases virus‐induced NFκB activation. Further, NFκB inhibition significantly suppresses host viability, suggesting a pro‐survival role for NFκB. Short‐term treatment of cells with tumour necrosis factor‐α (TNF‐α), a potent activator of NFκB, promotes host cell viability without affecting virus replication. However, a prolonged treatment has a detrimental effect on cells, indicating the existence of a delicate balance between the anti‐ and pro‐apoptotic roles of TNF‐α in the setting of CVB3 infection.