Tenets of viral carcinogenesis are summarized in Table 1.
Table1. Tenets of Viral Carcinogenesis
Tumor Viruses Are of Different Types Like other viruses, tumor viruses are classified among different virus families according to the nucleic acid of their genome and the biophysical characteristics of their virions. Most recognized tumor viruses either have a DNA genome or generate a DNA provirus after infection of cells (hepatitis C virus is an exception).
DNA tumor viruses are classified among the papilloma-, polyoma-, adeno-, herpes-, hepadna-, and poxvirus groups. DNA tumor viruses encode viral oncoproteins that are important for viral replication but also affect cellular growth control pathways.
Most RNA tumor viruses belong to the retrovirus family. Retroviruses carry an RNA-directed polymerase (reverse transcriptase) that constructs a DNA copy of the RNA genome of the virus. The DNA copy (provirus) becomes integrated into the DNA of the infected host cell, and it is from this integrated DNA copy that all proteins of the virus are translated.
RNA tumor viruses are of two general types with respect to tumor induction. The highly oncogenic (direct-transforming) viruses carry an oncogene of cellular origin. The weakly oncogenic (slowly transforming) viruses do not contain an oncogene and induce leukemias after long incubation periods by indirect mechanisms. The two known cancer-causing retroviruses in humans act indirectly. Hepatitis C virus, a flavivirus, does not generate a provirus and appears to induce cancer indirectly.
Multistep Carcinogenesis
Carcinogenesis is a multistep process; that is, multiple genetic changes must occur to convert a normal cell into a malignant one. Intermediate stages have been identified and designated by terms such as “immortalized,” “hyperplastic,” and “preneoplastic.” Tumors usually develop slowly over a long period of time. The natural history of human and animal cancers suggests a multistep process of cellular evolution, probably involving cellular genetic instability and repeated selection of rare cells with some selective growth advantage. The number of mutations underlying this process is estimated to range from five to eight. Observations suggest that activation of multiple cellular oncogenes and inactivation of tumor suppressor genes are involved in the evolution of tumors whether or not a virus is involved.
It appears that a tumor virus usually acts as a cofactor, providing only some of the steps required to generate malignant cells. Viruses are necessary—but not sufficient—for development of tumors with a viral etiology. Viruses often act as initiators of the neoplastic process and may do so by different mechanisms.
