Abstract
An etiologic role of neurotropic viruses in glioma is supported by epidemiologic and clinical observations. Glioma patients consistently report a lower history of clinical responses to varicella (VZV, chickenpox and shingles). Pathologic and clinical evidence for an active role of Cytomegalovirus (CMV) in gliomagenesis is also accumulating, though the subject remains controversial. We hypothesized that the neurotropic location of viral latency and subsequent patient-restricted response to these infections may impact efficacy of immune response against glioma, affecting incidence of the disease as well as survival in those afflicted. We explored the viral protein-restricted response against 99 VZV and 156 CMV protein antigens using Nucleic Acid Programmable Protein Arrays (NAPPA) in serum samples from 45 glioma patients and 45 controls from the University of California, San Francisco Adult Glioma Study (AGS). The proportion of agreement between the NAPPA positivity for CMV and VZV reactivity with traditional ELISA whole virus serological assay was 86% and 95%, respectively (Cohen's Kappa 0.72 and 0.9, respectively). Cases were more likely to have complex reactions to 5 or more antigens of VZV (p = 0.03). Cases reacted more strongly to specific proteins including Orf12, Orf14, and Orf49 (p < 0.03), and antigen recognition was strikingly stronger among cases for Orf23 and Orf9, a viral capsid and tegument protein, respectively. Multivariable analysis pointed towards significant differences between cases and controls for Orf9, Orf37, and Orf44. For CMV, protein reactivity was also stronger in cases for the specific proteins UL25, TRS1, and UL48a, also capsid and tegument proteins. Ongoing studies will assess (1) anti-VZV antigens in prediagnostic sera from glioma cases and matched controls in the PLCO cohort study and (2) the role of antibody reactions in survival of glioma patients within AGS. Specific differences in reactivity to these Herpesviruses may promote strategies for glioma prevention and therapies.
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