Natural Simian Virus 40 Strains Are Present in Human Choroid Plexus and Ependymoma Tumors

Abstract

Simian virus 40 (SV40) sequences for large tumor antigen (T-ag) were recently detected in a significant fraction of certain human brain tumors of early childhood (Bergsagel et al., N. Engl. J. Med. 326, 988-993, 1992). In the current study, we sought to determine whether authentic SV40 was present in the choroid plexus and ependymoma tumors previously examined. Polymerase chain reaction and DNA sequence analysis revealed authentic SV40 regulatory region and major capsid (VP1) sequences in 14 of 17 tumors tested. Only one 72-basepair element was detected in the SV40 enhancer region of positive tumor samples, an arrangement designated as "archetypal." The C terminus of the T-ag gene was detected in the same 14 tumors and was sequenced from 5 tumors; some nucleotide changes were found that would result in amino acid changes in T-ag. Infectious SV40 was isolated from one sample after lipofection of tumor DNA into monkey kidney cells. Sequence analysis of the rescued virus SVCPC revealed (i) an archetypal regulatory region, (ii) nucleotide changes in the C terminus of the T-ag gene that distinguished it from SV40 laboratory strains 776 and SV40-B2 and from human isolate SVPML-1, and (iii) identity with previous human brain tumor isolate SVMEN in the three genomic regions sequenced. No human-isolate-specific distinguishing features were detected among the viral sequences analyzed. Thus, authentic SV40 is present in humans and associated with two tumor types known to be induced experimentally by the virus.

Different simian virus 40 genomic regions and sequences homologous with SV40 large T antigen in DNA of human brain and bone tumors and of leukocytes from blood donors

“…Indeed, by using a semiquantitative PCR assay we determined 10 Ϫ2 to 10 Ϫ4 SV40 genome equivalents per cell in DNA samples from human lymphoproliferative disorders and from PBMCs of blood donors. 18 SV40 reactivation, by transfection of SV40 positive human DNA into permissive monkey cells, was reported in only a single case, 23 in agreement with the observation that in human cells that are semipermissive for SV40, this virus replicates poorly, 24 reaches low viral titers, 18,24,25 and generates at high-rate heterogeneous defective genomes, 26 which may interfere with the production of a complete, infectious viral progeny.…”

Integration of SV40 in human osteosarcoma DNA

“…Sequences from SV40 were also detected in normal tissue from six osteosarcoma patients (Carbone et al, 1996). Structural analysis of the SV40 origin of replication and the C-terminal Tantigen regions suggests that SV40 found in tumors are distinct non-laboratory strains (Stewart et al, 1996;Lednicky et al, 1995). Overall, these observations suggest that SV40 might have a role in the pathogenesis of human cancer, or at least have a tropism to certain tumors.…”

“…Disagreement exists about the presence of SV40 in normal peripheral blood lymphocytes; Bergsagel et al (1992) found no SV40 in 100 samples and Martini et al (1996) detected SV40 in four of 30 samples. Studies using PCR have found SV40 sequences in 50 ± 70% of mesotheliomas, 70 ± 90% ependynomas as well as astrocytomas and glioblastomas (Bergsagel et al, 1992;Martini et al, 1996;Carbone et al, 1994;Pepper et al, 1996;Lednicky et al, 1995). Others were unable to detect SV40 in mesotheliomas (Strickler et al, 1996).…”

Ependimomas: achados clínicos, epidemiológicos e anatomopatológicos de 22 casos

“…Há possível associação da transformação neoplásica das células ependimárias com infecção pelo vírus SV40, o que foi demonstrado pela identificação de fragmentos de DNA viral nas células neoplásicas, bem como pela detecção imuno-histoquímica do antígeno T grande 15 . Há descrições esporádicas da associação de ependimomas com facomatoses, síndrome endócrina múltipla tipo1 16 , síndrome da mutação de TP53 em células germinativas 17 e síndrome de Turcot 18 .…”