Coxsackievirus B3 activates nuclear factor kappa B transcription factor via a phosphatidylinositol-3 kinase/protein kinase B-dependent pathway to improve host cell viability.
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 (NFkappaB) transcription factor is involved in inflammation, survival and apoptosis. In this study, we investigated the role of NFkappaB 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 NFkappaB into the nucleus of infected cells. Inhibition of the PI3K/Akt pathway markedly decreases virus-induced NFkappaB activation. Further, NFkappaB inhibition significantly suppresses host viability, suggesting a pro-survival role for NFkappaB. Short-term treatment of cells with tumour necrosis factor-alpha (TNF-alpha), a potent activator of NFkappaB, 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-alpha in the setting of CVB3 infection.
Esfandiarei
Mitra
M
The James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, Providence Health Care Research Institute/St. Paul's Hospital, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
Boroomand
Seti
S
Suarez
Agripina
A
Si
Xiaoning
X
Rahmani
Maziar
M
McManus
Bruce
B
D021581:Active Transport, Cell Nucleus; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D029822:Enterovirus B, Human / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D016328:NF-kappa B / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014779:Virus Replication
D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt