Malignant glial neuronal tumors after west nile virus neuroinvasive disease

Abstract

Background: Acute West Nile Virus (WNV) infection can cause a spectrum of neurological disorders, including meningitis, encephalitis, and acute flaccid paralysis. Relatively little is described regarding the etiology of delayed neurological deficits or long-term sequelae in survivors of WNV neuroinvasive disease (WNND). Results: We present two cases of glial neuronal tumors in patients with severe WNND in which viral infection appears to have been a precursor to the development of aggressive brain tumors. We describe a potential mechanism where changes on a molecular signaling level by the WNV infection may result in tumor promotion. Conclusions: West Nile virus infection increases expression of pro-inflammatory and tumor-promoting proteins S100 calcium binding protein B (S100B), high-mobility group box-1 (HMGB1), and osteopontin (OPN). S100B and HMGB1 bind the receptor for advanced glycation end products (RAGE), a protein documented to be in overabundance in glial tumors. Activation of RAGE may contribute to proliferation and invasiveness of tumor cells. The presence of OPN in the tumor milieu, irrespective of its source, also leads to enhanced tumor growth and metastasis. To our knowledge, these are the first reported cases of their type. Given that WNV has the potential for altering cellular signaling at a molecular level and increasing expression of tumorigenic molecules known to be overexpressed in glial tumors, further investigations are warranted to clarify the relationship between these disease processes and potential risk for developing CNS neoplasm. In addition, there may be significant implications for brain tumor patients who develop WNV infection.