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Why do viruses cause cancer? Highlights of the first century of human tumour virology

Abstract

The year 2011 marks the centenary of Francis Peyton Rous's landmark experiments on an avian cancer virus. Since then, seven human viruses have been found to cause 10–15% of human cancers worldwide. Viruses have been central to modern cancer research and provide profound insights into both infectious and non-infectious cancer causes. This diverse group of viruses reveals unexpected connections between innate immunity, immune sensors and tumour suppressor signalling that control both viral infection and cancer. This Timeline article describes common features of human tumour viruses and discusses how new technologies can be used to identify infectious causes of cancer.

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Figure 1: Historical figures.
Figure 2: Common cellular targets for unrelated tumour virus oncoproteins.
Figure 3: Two views for the origins of viral oncoproteins.
Figure 4: The molecular evolution of a human tumour virus.

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Acknowledgements

The authors would like to thank G. Klein and O. Gjoerup for helpful comments and corrections to the manuscript; M. Melbye at the Danish Statens Serum Institut, and T. Söderqvist and his staff at the Medical Museion, University of Copenhagen, Denmark, for materials; and F. Zappa for help in preparing the manuscript. The authors are supported by NIH CA136363, CA120726, the Al Copeland Foundation, and American Cancer Society Research Professorships.

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Glossary

Antibody panning

cDNA from a tumour is used to express proteins in bacteria and transferred to replicate filters. Antibody screening of the filters can then be used to identify colonies expressing the specific cDNA encoding an antigen.

Bayesian reasoning

A scientific approach developed from Bayes theorem, combining features of the Logical Positivist and Kuhnian schools of science philosophy, and describing how the probability of a hypothesis (in this case, virus A causes cancer B) changes with new evidence. In simple terms, it can be described as the repeated application of the scientific method to falsify a hypothesis such that the hypothesis has a high probability of being either true or false.

Digital transcriptome subtraction

DTS. Method to discover new viruses by exhaustively sequencing cDNA libraries and aligning known human sequences by computer leaving a smaller candidate pool of potential viral sequences for analysis36.

Endogenous retrovirus

ERV. Retrovirus that has inserted into the metazoan germline genome over evolutionary timescales and is now transmitted to offspring as a genetic element through Mendelian inheritance. Approximately 8% of the human genome is estimated to be derived from retroviral precursors.

High-risk papillomaviruses

More than 160 different genotypes or strains of HPV have been described but only a few genotypes belonging to a high-risk carcinogenic clade of the α-HPV genus are responsible for invasive HPV-related anogenital cancers211.

Longitudinal study

Virus infection is measured initially in a cohort of patients who are then followed over time to determine cancer occurrence.

Prodromal phase

An early set of nonspecific symptoms that occur before the onset of specific disease symptoms.

Representational difference analysis

A PCR-based subtractive hybridization technique that can subtract common human sequences from a tumour genomic library using a control human tissue genomic library35.

Serology

The measurement of antibodies against viruses in blood or bodily fluids. This usually does not distinguish ongoing infections from past viral infections.

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Moore, P., Chang, Y. Why do viruses cause cancer? Highlights of the first century of human tumour virology. Nat Rev Cancer 10, 878–889 (2010). https://doi.org/10.1038/nrc2961

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