Journal of Neuro-Oncology

, Volume 95, Issue 1, pp 49–60 | Cite as

Detection of human herpesvirus-6 in adult central nervous system tumors: predominance of early and late viral antigens in glial tumors

  • John R. Crawford
  • Maria Rita Santi
  • Robbie Cornelison
  • Satu-Leena Sallinen
  • Hannu Haapasalo
  • Tobey J. MacDonald
Laboratory Investigation - Human/Animal Tissue


The purpose is to determine the incidence of active and latent human herpesvirus-6 (HHV-6) infection in a large cohort of adult primary and recurrent CNS tumors. We screened a tissue microarray (TMA) containing more than 200 adult primary and recurrent CNS tumors with known clinical information for the presence of HHV-6 DNA by in situ hybridization (ISH) and protein by immunohistochemistry (IHC). One hundred six of 224 (47%) CNS tumors were positive for HHV-6 U57 Major Capsid Protein (MCP) gene by ISH compared to 0/25 non tumor control brain (P = 0.001). Fourteen of 30 (47%) tumors were HHV-6 MCP positive by nested PCR compared to 0/25 non-tumor brain controls (P = 0.001), revealing HHV-6 Variant A in 6 of 14 samples. HHV-6A/B early (p41) and late (gp116/64/54) antigens were detected by IHC in 66 of 277 (24%) (P = 0.003) and 84 of 282 (35%) (P = 0.002) tumors, respectively, suggesting active infection. HHV-6 p41 (P = 0.645) and gp116/64/54 (P = 0.198) antigen detection was independent of recurrent disease. Glial tumors were 3 times more positive by IHC compared to non glial tumors for both HHV-6 gp116/64/54 (P = 0.0002) and HHV-6 p41 (P = 0.004). Kaplan Meier survival analysis showed no effect of HHV-6 gp116/64/54 (P = 0.852) or HHV-6 p41 (P = 0.817) antigen detection on survival. HHV-6 early and late antigens are detected in adult primary and recurrent CNS tumors more frequently in glial tumors. We hypothesize that the glial-tropic features of HHV-6 may play an important modifying role in tumor biology that warrants further investigation.


Human herpesvirus-6 Brain tumor Tissue microarray HHV-6 


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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • John R. Crawford
    • 1
    • 4
    • 8
  • Maria Rita Santi
    • 2
    • 4
  • Robbie Cornelison
    • 5
  • Satu-Leena Sallinen
    • 6
  • Hannu Haapasalo
    • 7
  • Tobey J. MacDonald
    • 3
    • 4
  1. 1.Department of NeurologyThe George Washington UniversityWashingtonUSA
  2. 2.Department of PathologyThe George Washington UniversityWashingtonUSA
  3. 3.Department of Hematology-OncologyThe George Washington UniversityWashingtonUSA
  4. 4.The Brain Tumor Institute, Children’s National Medical CenterThe George Washington UniversityWashingtonUSA
  5. 5.Molecular Genetics SectionThe National Cancer InstituteBethesdaUSA
  6. 6.Department of Pediatrics, Genetics Outpatient ClinicsTampere University HospitalTampereFinland
  7. 7.Department of PathologyTampere University HospitalTampereFinland
  8. 8.Department of NeurologyUniversity of California, San DiegoLa Jolla, San DiegoUSA

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