Expression of human neurotropic polyomavirus JCV late gene product agnoprotein in human medulloblastoma.
BACKGROUND
The human neurotropic polyomavirus, JCV, contains an open reading frame within the late region of the viral genome that encodes a 71-amino-acid protein, agnoprotein. Because accumulating evidence supports an association between JCV infection and human brain tumors, including medulloblastomas, we assessed the presence of JCV Agno gene sequences and the expression of agnoprotein in a series of 20 well-characterized medulloblastomas.


METHODS
Formalin-fixed, paraffin-embedded tumor tissue samples were used for Agno gene amplification and for immunohistochemical analysis. Adjacent sections were stained with an antibody to agnoprotein and with antibodies to cellular structural and regulatory proteins, including the JCV early gene product, T antigen.


RESULTS
Analysis of amplified DNA from paraffin-embedded samples revealed the presence of the Agno gene in 11 (69%) of 16 samples. Immunohistochemical analysis showed cytoplasmic localization and widespread distribution of agnoprotein in the neoplastic cells in 11 (55%) of 20 samples. The JCV early gene product, T antigen, was present in the nucleus of some, but not all, of the neoplastic cells. Some medulloblastoma samples that expressed agnoprotein had no sign of T-antigen expression. p53 was detected in only six of the 11 tumors in which agnoprotein was expressed. None of the 20 samples showed expression of the viral late capsid proteins, ruling out productive infection of the tumor cells with JCV.


CONCLUSIONS
Our data provide evidence that the JCV late gene encoding the auxiliary agnoprotein is expressed in tumor cells. The finding of agnoprotein expression in the absence of T-antigen expression suggests a potential role for agnoprotein in pathways involved in the development of JCV-associated medulloblastomas.
Del Valle
Luis
L
Center for Neurovirology and Cancer Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA.
Gordon
Jennifer
J
Enam
Sahnila
S
Delbue
Serena
S
Croul
Sidney
S
Abraham
Selvajothi
S
Radhakrishnan
Sujatha
S
Assimakopoulou
Martha
M
Katsetos
Christos D
CD
Khalili
Kamel
K
D001483:Base Sequence; D001932:Brain Neoplasms / Q000209:etiology / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007577:JC Virus / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification*; D008297:Male; D008527:Medulloblastoma / Q000209:etiology / Q000821:virology*; D008969:Molecular Sequence Data; D014764:Viral Proteins / Q000032:analysis* / Q000235:genetics; D054334:Viral Regulatory and Accessory Proteins; D000086082:Viroporin Proteins
D004279:DNA, Viral; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C042559:agnoprotein, polyomavirus; D000086082:Viroporin Proteins