Viral mechanisms of carcinogenesis

Several kinds of virus can cause cancer. The various viruses with oncogenic potential probably act through different mechanisms and depend on different host factors. The tumour viruses with small genomes are best understood and may be regarded as transposable genetic elements. By integrating into host cell chromosomal DNA, they may cause mutations and chromosomal rearrangements that predispose to cancer. The insertion of viral promoter sequences adjacent to certain host genes can lead to ectopic gene expression resulting in neoplasia. There is growing evidence, however, that the most strongly oncogenic strains of small DNA and RNA viruses carry 'oncogenes' that encode 'transforming' proteins. Papovavirus early proteins interact with cellular proteins involved in the control of cell proliferation. Many, but not all, of the transforming proteins of retroviruses are located at the plasma membrane and exhibit protein kinase activity, phosphorylating tyrosine residues. Most of the oncogenes of retroviruses studied so far are derived from cellular genes which may play important roles in regulating normal cell proliferation and differentiation. Retrovirus oncogenes may therefore be regarded as kidnapped host factors placed under the control of infectiously transmitted promoter elements. A variety of other host factors and exogenous cofactors affect the course of viral carcinogenesis, from influencing initial infection to immunological responses to chronic infection. Lastly, the endogenous viral genomes, which are inherited as host genetic elements, should themselves be considered as host factors that interact with exogenous carcinogens such as chemicals and ionizing radiation.