Historical Background and Zilber's Theory
The etiological link between viruses and tumors was first scientifically proven in 1910 when Peyton Rous established the viral nature of sarcoma in chickens. Subsequently, throughout the 1930s, researchers confirmed the involvement of specific filterable agents in the development of a range of pathologies: rabbit papillomas and skin carcinomas, mouse mammary carcinomas, and chicken lymphomas.
A key contribution to understanding the true nature of viral oncogenesis was made by the prominent researcher L.A. Zilber. In 1946, he published a comprehensive monograph titled The Viral Theory of the Origin of Malignant Neoplasms. The central postulate of his viral-genetic theory states that for malignant cellular transformation to occur, it is absolutely essential for the viral genome to integrate into the cellular genome and closely interact with it. In the 1970s, advances in molecular biology methods fully confirmed the validity of Zilber's theory.
Basic Principles of Oncovirus Classification
All oncogenic viruses share a proven ability to transform normal cells into malignant ones. They are typically classified by nucleic acid type and mode of transmission.
Based on genome type, two main categories are distinguished:
- RNA viruses: represented by the family Retroviridae. The mechanisms of viral oncogenesis have been most thoroughly and deeply studied using this group as a model.
- DNA viruses: include a broad range of families, among them Papillomaviridae, Polyomaviridae, Adenoviridae, Hepadnaviridae, Herpesviridae, and Poxviridae.
Based on their persistence in the organism and routes of spread, oncoviruses are divided into two large groups:
- Endogenous oncoviruses: act as permanent elements of the cellular genome and are stably present in all body tissues. They are transmitted vertically (from parents to offspring, like regular genes). Notably, they are typically non-oncogenic for their natural host in whose genome they reside.
- Exogenous oncoviruses: spread horizontally—that is, from an infected individual to a healthy one—and exist as fully infectious virions.
Molecular Mechanisms of Cellular Transformation
The biological basis of viral oncogenesis is the onc-gene theory. To understand the essence of the process, it is necessary to clearly distinguish between two basic states of the genetic apparatus:
- Proto-oncogenes: normal cellular genes that exist in an inactive (dormant) state. In a healthy cell, they regulate growth and division processes strictly.
- Oncogenes (onc genes): activated forms of proto-oncogenes that directly cause malignant cellular transformation. Modern science knows more than 20 types of such genes (examples include the src gene, which causes Rous sarcoma in chickens, and the ras gene, which causes sarcoma in rats).
A virus can activate a cellular proto-oncogene through several pathways:
- Insertional mutagenesis: integration of the provirus DNA into the cellular genome automatically activates a nearby proto-oncogene.
- Oncogene transduction: the provirus can excise from the chromosome, capturing a cellular onc gene, incorporating it into its own genome structure, and transferring it to the next cell in a hyperactivated form.
- Trans-activation: pathological enhancement of normal cellular gene transcription occurs under the influence of specific viral promoters or enhancers. These regulatory elements are located in the long terminal repeats (LTR) of the virus.
- Genetic rearrangement: integration of viral DNA leads to severe structural changes in the cellular genome, fatally disrupting the normal cell division cycle.
Note: Proto-oncogene activation can be triggered not only by oncogenic viruses but also by various mutagens and mobile genetic elements.
Physicochemical Properties
Oncogenic viruses exhibit specific resistance and sensitivity profiles to environmental factors. They possess high sensitivity to chemical reagents: they are rapidly destroyed by ether, detergents, and formalin. They are also completely inactivated by thermal exposure at 56 °C. At the same time, oncoviruses demonstrate high resistance to ultraviolet irradiation and tolerate low temperatures exceptionally well.