© 1999 by Oxford University Press
Journal of the National Cancer Institute, Vol. 91, No. 13, 1166A-1167,
July 7, 1999
© 1999 Oxford University Press
CORRESPONDENCE |
RESPONSE: Re: Cell and Molecular Biology of Simian Virus 40: Implications for Human Infections and Disease
Affiliation of authors: Division of Molecular Virology, Baylor College of Medicine, Houston, TX.
Correspondence to: Janet S. Butel, Ph.D., Division of Molecular Virology, Mail Stop BCM-385, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030.
Drs. Durie and Urnovitz make the important point that a combination of host and cellular responses must be considered when evaluating the possible involvement of viral exposure in human cancer development. The status of the host immune response is an important determinant, including not only antibody production but also cytotoxic T-cell responses. In addition to subtleties of the immune response, other undefined pertinent host factors include age effects on susceptibility to virus infection and tissue distribution of susceptible cells.
The authors point out that finding fingerprints of viruses is as meaningful as finding the entire viral genome for considering an etiologic involvement in tumorigenesis. This conclusion is substantiated by many studies of DNA virus carcinogenesis in model systems. Mounting evidence is now available that viral genes may be lost as tumor progression and accumulation of cellular genetic mutations make viral oncogene expression redundant (1-3). This process might reduce the number of genome copies of viral DNA to less than one per cell in a tumor sample.
Viral factors are also relevant to an evaluation of whether simian virus 40 (SV40) is a human tumor virus. Factors still to be examined include possible virus variants differing in oncogenic potential, modes of transmission among hosts, and possible restricted distribution of viral infections within geographic regions or human subpopulations. The detection of SV40 DNA in hospitalized children raises important questions about infection rates and sources of viral exposure in the population (4). Another ill-defined variable is the possible involvement of environmental carcinogens that might act synergistically with virus infection to induce cancer.
Rodent animal models, although invaluable in establishing that SV40 is a potent tumor virus, have limitations as predictors of the expected state of SV40 in human cancer. One major difference is that SV40 does not establish productive infections in rodents, as it does in many human cells. A recent report described the presence of episomal SV40 genomes in human transformed cells (5); although episomal gene copies have been detected in transformed rodent cells (6), the SV40 genome is usually integrated in the chromosomal DNA of those cells.
The biologic complexities pointed out by the correspondents remind us to be cautious in attempts to extrapolate directly from one viral system in humans to another. For example, although the human papillomaviruses are related to SV40, the biologies of the two groups of viruses are quite different, and the human papillomavirus-cervical cancer association cannot predict details of SV40 interactions with human tumors.
The complexities itemized above illustrate why different studies may draw conflicting conclusions regarding a viral association with a particular cancer, depending on the sources of samples analyzed, the procedures followed during sample preparation, and the specificity and sensitivity of test assays.
The possible role of SV40 in human cancer remains an intriguing and challenging question. The answers to this emerging public health puzzle will come gradually as different studies address host, cellular, and viral issues such as those highlighted above.
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