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PubMed1976

Viruses and cancer of the lower genital tract.

The importance of viruses as oncogenic agents in animals is well established. Recent work suggests that viruses may also be etiologically related to some human cancers. Herpes simplex virus type 2 (HSV-2) and the genital wart virus are prime suspects in carcinomas involving the female lower genital tract. In particular, a close association has been found between HSV-2 infection and cervical neoplasia in cytohistopathologic and seroepidemiologic studies. Preliminary results of prospective studies show further that women with genital herpetic infection are at increased risk of developing cervical neoplasia. Additional studies are also in progress on animal models, including subhuman primates, and efforts continue in the attempt to confirm the presence of viral genetic material or its expression in human cervical cancer cells. The possibility that human wart viruses have an oncogenic potential is suggested by clinicopathologic and electron microscopic observations. Further research is needed to ascertain the precise role of viruses in genital cancer.

Adenoviridae↗
PubMed1977

The morphology of human papillomas of the upper respiratory tract.

Recurrent squamous papillomas of the upper respiratory tract were examined by light microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Surface of the cells is irregular and is covered by numerous stout microvilli. These are shorter and broader than those of cells of the uninvolved mucosa. The villi often seem umbilicated at the apex; the remainder of them, however, are rounded. The epithelium participating in the formation of papillomas shows some maturation of the cells but this does not progress normally. The predominating area is the thickened spinous layer representing the bulk of the lesion. The basal layer shows mildly increased activity but the basement membrane is intact. The cells often are very closely packed but in some areas, more particularly in the deep layer, they are loosely arranged. The intercellular space contains a moderately electron-dense finely fibrillar material. No abnormal mitoses are found. The neighboring univolved epithelium often shows increased growth activity and some inflammation. The larygneal papillomas propably represent an overgrowth of epithelium which may develop following hindered desquamation caused and/or heralded by a chronic inflammatory condition probably of viral origin and may be preceded by epithelial metaplasia and hyperplasia.

Adult↗
PubMed1982

Distribution of papovavirus, myelin-associated glycoprotein, and myelin basic protein in progressive multifocal leukoencephalopathy lesions.

To study how viruses interact with oligodendroglia and produce demyelination, we immunostained paraffin and epon sections of lesions from patients with progressive multifocal leukoencephalopathy (PML) with antisera to papovaviruses, oligodendroglial myelin-associated glycoprotein (MAG), and myelin basic protein (MBP) according to the peroxidase-antiperoxidase method. In paraffin sections from a rapidly progressive case of PML, hyperimmune JC virus antiserum stained single oligodendroglia which were located in white matter that appeared normal histologically and stained normally with MAG and MBP antisera. In zones surrounding areas of demyelination, virus containing oligodendroglia were most numerous and MAG staining of periaxonal regions was decreased, but there was little change in MBP staining. In demyelinated regions, both MAG and MBP staining were severely altered; also there was much less JC virus staining. In tissue from three other chronic cases, viral antiserum stained fewer oligodendrocytes and the differences in MAG and MBP staining were much less striking. In epon sections from two biopsies of central nervous system tissue, we studied the electron microscopic appearance of oligodendroglia that also had been stained by JC virus antiserum. Virions were present in all nuclei and in some cytoplasmic regions. The results suggest that changes in MAG distribution are useful indicators of early oligodendroglial abnormalities which can cause myelin breakdown.

Aged↗
PubMed1977

Interspecies-, species- and type-specific T antigenic determinants of human papovaviruses (JC and BK) and of Simian virus 40.

Immunofluorescence tests, absorption studies and quantitative analysis by a very sensitive 51Cr microcomplement fixation (CF) technique were used to define the degree of relatedness between the tumor (T) antigens induced by human papovaviruses, strain JC and BK, with simian virus 40(SV40) and mouse polyoma virus (PyV). Antisera against JCV, BKV, SV40 and PyV T were raised in tumor-bearing hamsters. The data obtained indicate that T antigens of JCV, BKV and SV40 possess various subspecificities which can be distinguished and looked upon as interspecies-, species- and type-specific antigenic determinants. It was found that JCV T and BKV T synthesized in transformed hamster cells share about the same amount (20%) of interspecies cross-reacting antigen with SV40 T from H-50 cell extracts (transformed hamster cells). Although hamster cells transformed by PyV showed definite PyV T reactivity, no cross-reactivity, at least with the sera used, was found with human papovavirus and SV40 T antigens. Furthermore, degree of heterogeneity was observed within the T antigen complex derived from different SV40-transformed cells.

Animals↗
PubMed1978

Microfluorometric analysis of anti-complement and indirect immunofluorescence tests for human papovavirus (JCV and BKV) T antigens.

The anti-complement immunofluorescence (ACIF) test was compared with the conventionally used indirect IF (IIF) in regard to its usefulness for the detection of low amounts of human papovavirus tumor (T) antigen. Fluorescence microscopic analysis revealed that it is significantly more sensitive. Microfluorometric measurements on the intensity of staining of T-antigen-positive nuclei demonstrated that JCV T in HJC-15 cells was 35-fold and BKV T in BK-L3 cells 94-fold more intensively stained in the ACIF then in the IIF. It appears that the lower the actual amount of a given antigen the more valuable is the ACIF test.

Animals↗
PubMed1979

Isolation of a SV40-like Papovavirus from a human glioblastoma.

A human glioblastoma multiforme (M27) tested in early cell cultures by indirect immunofluorescence staining showed SV40-related tumor (T)-antigen, 95% of the cells being positive. SV40-related viral capsid (V)-antigen was absent in all cells tested. Experiments to rescue this virus were performed by fusing M27 cells with CV-I monkey cells, which were permissive for SV40, using polyethylene glycol (PEG) as fusion factor. We succeeded in isolating virus particles SV40-GBM which electron microscopy showed to correspond in size and morphology to papovaviruses. Serological tests (hemagglutination, neutralization, fluorescent antibody) revealed that the virus is indistinguishable from SV40. Despite this apparent antigenic identity SV40-GBM differs slightly from SV40 wild type. This virus can propagate and produce CPE in both CV-I cells and primary fetal human kidney cells. Furthermore digestion of SV40-GBM DNA with the HindII/III restriction endonucleases revealed minor differences compared with the SV40 DNA. Therefore the virus SV40-GBM obtained from glioblastoma cells seems to be closely related to the SV40-PML viruses described earlier.

Antigens, Viral↗
PubMed1984

Monoclonal antibodies against simian virus 40 nuclear large T tumour antigen: epitope mapping, papova virus cross-reaction and cell surface staining.

Thirty six cloned hybridomas have been isolated which produce monoclonal antibodies directed against simian virus 40 (SV40) large T tumour antigen. They have been shown to recognize at least six different epitopes along the T antigen polypeptide according to their reaction with the various truncated forms of T antigen expressed by adenovirus-SV 40 hybrid viruses. Sixteen antibodies cross-react with cells infected by the closely related human BK virus. Only two antibodies, PAb1604 and PAb1614, directed against different epitopes of the SV40 T antigen, cross-react with polyoma large T tumour antigen which has a more limited amino acid sequence homology. This cross-reaction is rarely seen with polyclonal antibodies. Monoclonal antibody PAb1620 gave nuclear immunofluorescence only with murine cells transformed by SV40 and was found to react with a complex of T-antigen and 53 000-dalton host-coded protein. All the monoclonal antibodies react with nuclear T antigen and all but four antibodies stained the surface of SV40-transformed cells. These were four of the five antibodies directed against the central third of the T antigen. Thus the monoclonal antibodies show that cell surface T antigen differs from nuclear T antigen, either in accessibility or structure.

Animals↗
PubMed1985

A new member of the polyomavirus family: the hamster papovavirus. Complete nucleotide sequence and transformation properties.

The hamster papovavirus (HapV) is associated with multiple skin epitheliomas of the Syrian hamster. We have sequenced its genome. It is a double-stranded circular DNA of 5366 bp. The hypothetical genomic organization deduced from this nucleotide sequence is clearly of the polyoma type with the two strands coding in the opposite directions from a noncoding region that shows some of the features of a replication origin and a transcription control region. The amino acid sequences predicted from the open reading frames show an average of 50% homology with polyoma-coded polypeptides. The HapV is, after polyoma, the second example of a papovavirus coding for a middle T antigen. The cloned DNA can immortalize primary rat embryo cells and transform an established rat cell line. The viral DNA is stably integrated into the host genome.

Animals↗
PubMed1992

Cell specificity of transcription regulation by papovavirus T antigens and DNA replication.

Simian virus 40 (SV40) and polyomavirus (Py) DNA replication require cellular proteins and a virus-encoded early gene product, large T antigen (SVT and PyT, respectively). Primate cells contain factors permissive for SV40 replication, whereas murine cells express those factors permissive for Py. We have compared the roles T antigen, cell permissiveness and replication play in transcription of SV40 and Py genes. We show that in their respectively permissive cells, SV40 replication causes a major shift in transcription initiation from the early to the late viral promoter, whereas when Py replicates a comparable shift does not occur. This difference is discussed in relation to differences in the organization of the origin and promoter region between these two papovaviruses. Reporter plasmids were constructed that carried both viral origins, one at the natural position in the promoter being tested and the other at a distal location. With the appropriate TAg, these vectors could be made to replicate in either primate (HeLa) or rodent (3T6) cells. The SV40 early to late shift occurred when replication was driven in HeLa cells, and was not seen on replicating templates in rodent cells. Thus, replication per se does not account for the shift. We show also that, like SVT, PyT is a potent activator of transcription, and that SVT and PyT can activate each other's late promoters independently of DNA replication, but only in cells permissive for DNA replication catalysed by the respective T antigen. Taken together, the data presented here suggest that papovaviruses may utilize permissive factors in transcription control mechanisms.

Animals↗
PubMed1984

Oncogenes: growth regulation and the papovaviruses polyoma and SV40.

Cellular oncogenes and their activated and retrovirus-coded counterparts play an important role in cellular regulation. Here the relationship between such oncogenes and the genes coding for the transforming proteins of the papovaviruses, polyoma viruses, and simian virus 40 (SV40) is discussed. It is concluded that polyoma virus may transform established cells by a mechanism involving activation of a cellular oncogene product, whereas SV40 may transform by a mechanism involving a previously little studied cytoplasmic form of the transforming protein.

Animals↗
PubMed1981

B-lymphotropic papovavirus and possibility of infections in humans.

A novel member of the papovavirus group has been isolated from EBV-transformed African green monkey (AGM) B-lymphoblasts. The virus is characterized by its B-lymphotropic host range and has tentatively been named "lymphotropic papovavirus" (LPV). Seroepidemiological studies revealed that besides sera from African green monkeys a substantial proportion of human sera reacted with antigens of this virus. The specificity of this reaction observed in indirect immunofluorescence tests was underlined by immunoprecipitation (IP) and neutralization studies. By IP we demonstrated that AGM as well as human sera reacting in immunofluorescence with LPV antigens precipitated polypeptides of about 40 K. Those polypeptides were detected only in LPV-infected cultures. Sera of high reactivity in immunofluorescence tests also neutralized viral infectivity. These data suggest that an agent antigenetically closely related to AGM-LPV also infects part of the human population. The age distribution of the human antibody response revealed that a low percentage of sera reacted in age groups below 30 years. Thereafter, however, about 30% of all sera exhibited antibodies to LPV antigens. There was a slight increase in seroreactivity in sera from patients tested for infectious hepatitis when compared to non-selected human sera.

Age Factors↗