Importin-β and exportin-5 are strong biomarkers of productive reoviral infection of cancer cells

Gerard Nuovo, Hue Tran, Andres Gutierrez, Paolo Fadda, Flavia Pichiorri, Enrico Caserta, Craig C. Hofmeister, Marta Chesi, Peter Leif Bergsagel, Don Morris, Qiao Shi, Matt Coffey, Chandini Thirukkumaran

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

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 importin-β 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 importin-β 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 importin-β 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 anti-apoptotic 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 importin-β and exportin-5 levels which may serve as biomarkers of the disease in clinical specimens.

Original languageEnglish (US)
Pages (from-to)28-34
Number of pages7
JournalAnnals of Diagnostic Pathology
Volume32
DOIs
StatePublished - Feb 1 2018

    Fingerprint

Keywords

  • Exportin
  • Importin
  • Infection biomarkers
  • Multiple myeloma
  • Oncolysis
  • Reovirus

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Nuovo, G., Tran, H., Gutierrez, A., Fadda, P., Pichiorri, F., Caserta, E., Hofmeister, C. C., Chesi, M., Bergsagel, P. L., Morris, D., Shi, Q., Coffey, M., & Thirukkumaran, C. (2018). Importin-β and exportin-5 are strong biomarkers of productive reoviral infection of cancer cells. Annals of Diagnostic Pathology, 32, 28-34. https://doi.org/10.1016/j.anndiagpath.2017.10.001