Detection of human herpesvirus-6 in adult central nervous system tumors: predominance of early and late viral antigens in glial tumors.
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.
Department of Neurology, The George Washington University, 111 Michigan Ave NW, Washington, DC, 20010, USA. jrcrawford@ucsd.edu.|The Brain Tumor Institute, Children's National Medical Center, The George Washington University, 111 Michigan Ave NW, Washington, DC, 20010, USA. jrcrawford@ucsd.edu.|Department of Neurology, University of California, San Diego, 9500 Gilman Drive, La Jolla, San Diego, CA, 92093, USA. jrcrawford@ucsd.edu.
John R
JR
Crawford
Department of Pathology, The George Washington University, 111 Michigan Ave NW, Washington, DC, 20010, USA.|The Brain Tumor Institute, Children's National Medical Center, The George Washington University, 111 Michigan Ave NW, Washington, DC, 20010, USA.
Maria Rita
MR
Santi
Molecular Genetics Section, The National Cancer Institute, 9000 Rockville Pike, Bethesda, MD, 20892, USA.
Robbie
R
Cornelison
Department of Pediatrics, Genetics Outpatient Clinics, Tampere University Hospital, P.O. Box 2000, Tampere, 33521, Finland.
Satu-Leena
SL
Sallinen
Department of Pathology, Tampere University Hospital, P.O. Box 2000, Tampere, 33521, Finland.
Hannu
H
Haapasalo
Department of Hematology-Oncology, The George Washington University, 111 Michigan Ave NW, Washington, DC, 20010, USA.|The Brain Tumor Institute, Children's National Medical Center, The George Washington University, 111 Michigan Ave NW, Washington, DC, 20010, USA.
Tobey J
TJ
MacDonald
D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D000956:Antigens, Viral / Q000032:analysis / Q000235:genetics / Q000276:immunology; D000071178:CD48 Antigen; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism; D016543:Central Nervous System Neoplasms / Q000235:genetics* / Q000401:mortality / Q000821:virology*; D005910:Glioma / Q000235:genetics* / Q000401:mortality / Q000821:virology*; D015654:Herpesvirus 6, Human / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D016019:Survival Analysis; D014759:Viral Envelope Proteins / Q000378:metabolism
D015703:Antigens, CD; D000956:Antigens, Viral; D000071178:CD48 Antigen; D036022:Capsid Proteins; D014759:Viral Envelope Proteins