JC virus large T protein transforms rodent cells but is not involved in human medulloblastoma

Abstract

JC virus (JCV) together with Simian virus 40 (SV40) and BK virus (BKV), belong to the polyomavirus group and these viruses are neuro-oncogenic to rodents by expression of large T antigen (LT), which binds to cellular p53 and pRB thus reducing the anticancer potential of the cell. The function of LT has not been clarified because small t antigen (st) is transcribed from the same start codon as the overlapping reading frame of LT, and is translated as a different protein with the same N-terminal residues (1-81 amino acids) by a splice-site variant of mRNA. To elucidate the function of LT without st, we constructed plasmids that express LT only by deleting the splicing region including the C-terminus of st, and consequently stable cell lines were established that express only JCLT, SV40LT and BKLT. The growth rates of these cells were examined in colonies on soft agar and it was found that LT alone has a transforming capacity; the order of efficiency being SV40LT, BKLT and JCLT. In addition, to verify the involvement of JCV in human medulloblastoma, eight cases of medulloblastoma, six cases of frozen material and five cases of paraffin-embedded tissues which included three cases of frozen tissues, were examined. PCR assay, genomic Southern blotting, and in situ hybridization were applied to detect the JCV genome, and LT and st were examined by immunohistochemistry; the results were compared with JCV-infected tissues as a positive control. All methods failed to detect not only JCV genome but also LT protein in medulloblastoma and it was concluded that JCV LT has transforming activities in rodent cells, but is not related to human medulloblastoma.

Molecular Biology, Epidemiology, and Pathogenesis of Progressive Multifocal Leukoencephalopathy, the JC Virus-Induced Demyelinating Disease of the Human Brain

“…These observations remain somewhat controversial, as other reports indicate that JCV is not the causative agent of these tumors (186,241,349,509). Interestingly, p53 was reported to be colocalized in the nucleus with T antigen, suggesting that the interaction of T antigen with p53 may abrogate the role of p53 in control of cell proliferation.…”

Pathogenesis and Management of Polyomavirus Infection in Transplant Recipients

“…However, the recent demonstration of SV40 genomes in some cancers and nonmalignant diseases in humans suggests that the virus may be etiologically meaningful in the development of those diseases [3]. Polyomaviruses JCV and BKV also have the ability to induce tumors in laboratory animals [2,18], and they have been associated with some solid tumors in humans (in particular, brain cancers) [18][19][20], although less frequently than has SV40 [1,3].…”

Medulloblastomas and primitive neuroectodermal tumors rarely contain polyomavirus DNA sequences

“…In another European study that included 17 medulloblastomas, SV40 DNA sequences were detected in 5 (29%) specimens, BKV sequences in 1 (6%), and JCV sequences in none with PCR ampli cation and Southern methods (Huang et al, 1999). A Japanese group described negative results for JCV sequences in 8 medulloblastoma specimens; 6 by PCR ampli cation and Southern blotting, and 2 by in situ hybridization and immunostaining (Hayashi et al 2001). In contrast, North American investigators reported that 22 of 23 (96%) medulloblastomas contained JCV DNA sequences, and 5 of 23 (22%) also contained SV40 sequences.…”

“…Recently, different groups have reported discordant results regarding the detection of SV40, JCV, and BKV DNA sequences in human medulloblastomas (Hayashi et al, 2001;Huang et al, 1999;Krynska et al, 1999;Weggen et al, 2000).…”