GENERAL MICROBIOLOGY - T.P. Pyrog - 2004

10. VIRUSES: DISTRIBUTION AND STRUCTURE

10.4. THE ROLE OF VIRUSES AND PLASMIDS IN TUMOR FORMATION (ONCOGENESIS)

The onset of malignant (cancerous) tumors can be triggered by various factors, but in all cases, The Cell's genetic material—its DNA—is involved. The Transformation of a normal cell into a malignant one (a phenomenon known as tumor transformation) is fundamentally driven by some form of DNA alteration. Changes in the DNA of a normal cell can be caused by Viruses and Plasmids (circular extrachromosomal DNA molecules capable of cell-to-cell transfer). One of the underlying reasons is that both Plasmids and Viruses (in the form of a prophage) can integrate into the chromosomal DNA. Let us examine Examples of oncogenesis: tumor formation in plants; tumor development in animals induced by DNA viruses; and tumor development in animals induced by RNA viruses (Retroviruses).

Tumor formation in plants. Crown gall tumors occur in many plant species. These tissue overgrowths impair the flow of nutrients between the underground and aerial PARTS OF THE plant. The CAUSATIVE AGENT OF the tumor is Agrobacterium tumefaciens, a Gram-negative soil bacterium. There are both virulent and avirulent strains of Agrobacterium tumefaciens. Virulent

strains contain a large plasmid, the so-called Ti-plasmid, which is capable of integrating into the chromosomal DNA of PLANT Cells AND inducing tumor growth.

Oncogenesis in animals induced by DNA viruses. Studies on animal carcinogenesis are typically conducted using tissue cultures. When animal cells, such as those from chicken or hamster Organs, or human fibroblasts, are transferred into an appropriate nutrient medium, they begin to proliferate on the inner surface of the culture vessel. As a rule, cells grow until they come into contact with one another. Due to contact inhibition, only a single-layer cell sheet (monolayer) is formed. However, if these normal cells are infected with an oncogenic virus, contact inhibition is abolished, and the cells continue to proliferate, piling up on top of one another. Multilayer growth is observed exclusively in cells that have undergone tumor transformation.

Polyomavirus and SV40 (simian virus 40) belong to the papovavirus group. They contain double-stranded circular DNA molecules. In experimental settings, the virus can be introduced into tissue culture cells for propagation. When replicating in certain cells (referred to as permissive cells), the virus causes their lysis, resulting in cell death as the viral infection progresses. In other (non-permissive) cells, the virus behaves differently. In this case, viral Replication is suppressed, and only in about 1 out of 10⁵ cells does the viral DNA integrate into the cellular DNA. Such incorporation of viral DNA into the host cell genome may be accompanied by tumor transformation. The transformed cell synthesizes a protein (T-antigen) that triggers cellular METABOLISM/36.html">DNA replication, initiating cell proliferation. Injection of such transformed cells into animals leads to the rapid formation of tumors.

Oncogenesis in animals induced by RNA viruses. RNA viruses—specifically retroviruses—can also be implicated in tumor formation in animals. They belong to enveloped icosohedral viruses and possess a (+)RNA genome (single-stranded RNA). They cause Rous Sarcoma in chickens and leukemia in mice. The term "retroviruses" stems from the fact that their replication involves the enzyme Reverse Transcriptase. The RNA of these viruses cannot be reproduced through simple replication. An obligatory step is the preliminary Transcription of RNA into DNA, followed by the integration of this DNA into one of the host cell's Chromosomes. Integration is an essential step for the reproduction of this virus; only integrated viral DNA will be transcribed. Since integration into cellular DNA is part of the viral life cycle, the frequency of integration is very high. Apparently, viral DNA can incorporate into the cellular genome at virtually any site.

Viral replication does not lead to cell lysis. The nucleocapsid is assembled inside the cell, then migrates to The Plasma Membrane and exits the cell, acquiring an envelope derived from this membrane. The integrated retroviral genome replicates along with the host cell genome and is therefore present in every tumor cell. Tumor growth is driven by the expression (synthesis) of the viral onc Gene. This gene encodes a protein that presumably participates in converting a differentiated cell into an embryonic-type cell.

Viroids. The causative agents of certain plant tumors are small, naked—meaning devoid of a protein coat—free RNA molecules known as viroids. They are single-stranded, covalently closed circular molecules with a chain length of approximately 360 NUCLEOTIDES (with a Molecular Weight of 12·10⁴ daltons).

Consequently, they are 10 times smaller than the infectious RNAs of the smallest viruses. Viroids represent the smallest known disease agents. They cause diseases in potatoes, citrus fruits, cucumbers, chrysanthemums, hops, coconut palms, and other plants.