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.
Crawford
John R
JR
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.
Santi
Maria Rita
MR
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.
Cornelison
Robbie
R
Molecular Genetics Section, The National Cancer Institute, 9000 Rockville Pike, Bethesda, MD, 20892, USA.
Sallinen
Satu-Leena
SL
Department of Pediatrics, Genetics Outpatient Clinics, Tampere University Hospital, P.O. Box 2000, Tampere, 33521, Finland.
Haapasalo
Hannu
H
Department of Pathology, Tampere University Hospital, P.O. Box 2000, Tampere, 33521, Finland.
MacDonald
Tobey J
TJ
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.
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