Journal
ANNALS OF DIAGNOSTIC PATHOLOGY
Volume 32, Issue -, Pages 28-34Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.anndiagpath.2017.10.001
Keywords
Infection biomarkers; Importin; Exportin; Reovirus; Oncolysis; Multiple myeloma
Categories
Funding
- Alzheimer's disease Drug Discovery Foundation [20160204]
- Cancer Research Society of Canada, Oncolytics Biotech Inc.
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Acute reoviral infection has been extensively studied given the virus's propensity to target malignant cells and activate caspase-3 mediated apoptosis. Reovirus infection of malignant N1E-115 mouse neuroblastoma cells led to significant increased expression of importing) and exportin-5 mRNAs (qRTPCR) and proteins (immunohistochemistry) which was partially blocked by small interfering LNA oligomers directed against the reoviral genome. Co-expression analysis showed that the N1E-115 cells that contained reoviral capsid protein had accumulated importing) and exportin-5, as well as activated caspase 3. Reoviral oncolysis using a syngeneic mouse model of multiple myeloma similarly induced a significant increase in importing) and exportin-5 proteins that were co-expressed with reoviral capsid protein and caspase-3. Apoptotic proteins (BAD, BIM, PUMA, NOXA, BAK, BAX) were increased with infection and co-localized with reoviral capsid protein. Surprisingly. the antiapoptotic MCL1 and bcl2 were also increased and co-localized with the capsid protein suggesting that it was the balance of pro-apoptotic molecules that correlated with activation of caspase-3. In summary, productive reoviral infection is strongly correlated with elevated importing) and exportin-5 levels which may serve as biomarkers of the disease in clinical specimens.
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