Viruses and Human Cancer
Summary of Key Points
• More than 15% of human cancers are known today to be caused by viruses.
• A hallmark of virally induced cancers is that they are associated with persistent viral infections.
• Although some viruses encode oncogenes that directly contribute to the cancers they cause, other viruses are thought to result in cancer indirectly by causing chronic destruction of the target organ from which the cancer arises.
• The etiologic role of viruses in cancer is established through a combination of epidemiological and molecular evidence.
• In many cases, the cancers caused by the virus represent dead-end streets for the virus; that is, the virus is no longer able to replicate in the cancer.
• Virally induced cancers can be prevented through the use of effective prophylactic vaccines.
• Viral genes expressed in associated cancers represent targets for therapeutic vaccines and viral-specific anticancer drugs.
1. You identify the presence of a new virus in a human cancer. You further learn that certain viral genes are expressed in this cancer. What criteria would you use to establish a causal role for the virus in this cancer?
A Epidemiological evidence for an association of the virus with this cancer
B Determine if the viral genes expressed transform cells in tissue culture
C Determine if the viral genes expressed can induce tumors in an animal model
D Determine if the continued expression of the viral genes is necessary for the maintenance of the tumor phenotype
2. You discover that a cancer is increased in its incidence in patients with AIDS. You screen this cancer for known human viruses but find none present in the cancer. What would you do to learn if this cancer is caused by a yet-to-be-identified virus?
A Look for the presence of virus-like particles in the cancer; if they are present, isolate and sequence the viral genome and see if it transforms cells in tissue culture.
B Perform deep sequencing to look for nonhuman sequences present in the cancer; clone the genome and see if it transforms cells in tissue culture.
C Make an extract of the cancer, filter it to obtain a filtrate of subcellular-sized material, and see if this causes cancer in humans.
3. You identify a novel virus. To test its role in the cancer, you knock down expression of the viral genes expressed in cells derived from this cancer, but you find that the cancer cells are still transformed and grow as tumors in immunodeficient mice. Do you conclude that the virus does not cause cancer?
4. What ways can one use to prevent infections by a virus that causes cancer in the human population?
1. Answer: E. The etiologic role of viruses in cancer is based on a combination of epidemiological and molecular evidence.
2. Answer: E. In some cases, virus particles can be found (e.g., Epstein-Barr virus in Burkitt lymphoma). Deep sequencing provides perhaps the most sensitive way to identify novel viruses and does not depend on the cancer being able to produce virus particles. Performing infectious studies in humans is not ethical.
3. Answer: B. The virus might still be contributing to the cancer. An example is hepatitis V virus (HBV), which is etiologically associated with hepatocellular carcinoma (HCC). Although HBV genes are sometimes found expressed in this cancer, their expression is not required for the maintenance of the tumor phenotype. This phenomenon could be because the virus indirectly causes cancer (e.g., by causing cirrhosis, as in the case of HBV-associated HCC), or it could be because the viral genes were contributing to establishment of the cancer but not its maintenance.
4. Answer: F. All options except for a therapeutic vaccine will prevent infections. A therapeutic vaccine is used to eliminate existing infections.
