Detection of human herpesvirus-6 variants in pediatric brain tumors: Association of viral antigen in low grade gliomas

Background: Human herpesvirus-6 (HHV-6) has been associated with a diverse spectrum of central nervous system (CNS) diseases and reported glial tropism. Objective: To determine if HHV-6 is present in a series of pediatric brain tumors. Study design: Pediatric gliomas from 88 untreated patients represented in a tissue microarray (TMA) were screened for HHV-6 by nested polymerase chain reaction (PCR), in situ hybridization (ISH), and immunohistochemistry (IHC) and compared to non-glial tumors (N = 22) and control brain (N = 32). Results were correlated with tumor grade and overall survival. Results: HHV-6 U57 was detected by nested PCR in 68/120 (57%) tumors and 7/32 (22%) age-matched non-tumor brain (P = 0.001). HHV-6 U31 was positive in 73/120 (61%) tumors and 11/32 (34%) controls (P = 0.019). Seventy-two percent (43/60) of tumors were HHV-6 Variant A. HHV-6 U57 was confirmed by ISH in 83/150 (54%) tumors and 10/32 (31%) controls (P = 0.021), revealing a non-lymphocytic origin of HHV-6. HHV-6A/B gp116/64/54 late antigen was detected by IHC in 50/124 (40%) tumors and 6/32 (18%) controls (P = 0.013). Interestingly, 58% of low grade gliomas (N = 67) were IHC positive compared to 19% of high grade gliomas (N = 21, P = 0.002) and 25% of non-gliomas (N = 36, P= 0.001). HHV-6A/B gp116/64/54 antigen co-localized with glial fibrillary acidic protein, confirming the astrocytic origin of antigen. Overall, there was no primary association between HHV-6A/B gp116/64/54 antigen detection and survival (P = 0.861). Conclusions: We provide the first reported series of HHV-6 detection in pediatric brain tumors. The predominance of HHV-6 in glial tumors warrants further investigation into potential neurooncologic disease mechanisms. (C) 2009 Elsevier B.V. All rights reserved.