Infections by a number of viruses do not result in eventual host cell death, but rather cause tumor transformation of the cell. This means the cell is altered in many ways, e.g., in its growth properties, morphology, and metabolism.
Following infection with DNA tumor viruses, the type of host cell infected determines whether the cell reaction will be a tumor transformation, viral replication or lytic cycle. The transformation that takes place after infection with an RNA tumor virus either involves no viral replication (nonpermissive infection) or the cell produces new viruses but remains vital (permissive infection).
Genome structure and replication of the oncoviruses
The genomes of all oncoviruses possess gag (group-specific antigen), pol (enzymatic activities: polymerase complex with reverse transcriptase, integrase, and protease), and env (envelope glycoproteins) genes. These coding regions are flanked by two control sequences important for regulatory functions called LTR (= long terminal repeats).
These sequences have a promoter/enhancer function and are responsible for both reverse transcription and insertion of the viral genome into the cell DNA. Certain oncoviruses possess a so-called “onc gene” instead of the pol region (onc gene = oncogene, refers to a cellular gene segment acquired by recombination, see below).
These viruses also often have incomplete gag and/or env regions. Such viruses are defective and require a helper virus to replicate (complementation, see p. 391). An exception to this principle is the Rous sarcoma virus, which possesses both an onc gene and a complete set of viral genes and can therefore replicate itself.
Over 100 onc genes (so-called “oncogenes”) have been found in the course of tumor virology research to date. These genes enable tumor viruses to transform their host cells into tumor cells. The various types of oncogenes are designated by abbreviations, in most cases derived from the animal species in which the virus was first isolated.
Further investigation of these viral oncogenes have now shown that these genes are not primarily of viral origin, but are rather normal, cellular genes widespread in humans and animals and acquired by the oncoviruses in their host cells, which can be transferred to new cells (transduction). Such a cellular gene, not oncogenic per se, is called a proto-oncogene
The normal function of the proto-oncogenes concerns the regulation of cell growth in the broadest sense. Their gene products are growth factors, growth factor or hormone receptors and GTP-binding or DNA-binding proteins. Proto-oncogenes are potential contributors to tumor development that have to be “activated” before they can actually have such effects.
This can occur by way of several different mechanisms: — Chromosomal translocation: proto-oncogenes are moved to different chromosomes and thus placed under the influence of different cellular promoters, resulting in a chronic overexpression of the corresponding protein. — Mutation of the proto-oncogene. — Transduction of the proto-oncogene by an oncovirus. The oncovirus promoter may induce overexpression of the proto-oncogene, resulting in a tumor.
Tumor induction by oncoviruses.
Both types of carcinogenic retroviruses, i.e., those with no oncogene and intact replication genes (gag, pol, env, flanked by the LTR regions) and those that have become defective by taking on an oncogene, can initiate a tumor transformation. On the whole, oncoviruses play only a subordinate role in human tumor induction.
This is a slow process (e.g., chronic leukemias) in which cocarcinogens can play an important role. The transformed cells produce new viruses.