RNA Tumor Viruses (World of Microbiology and Immunology)
RNA tumor viruses contain ribonucleic acid as their genetic material. The viruses derive their designation from their association with tumors.
RNA tumor viruses are retroviruses that possess the reverse transcriptase enzyme that manufactures deoxyribonucleic acid (DNA) from the RNA template. Indeed, retro is the Latin word for backwards.
The history of RNA tumor viruses extends back to the first decade of the twentieth century. In 1908, it was demonstrated that fluid from a chicken that has leukemia could cause cells to be cancerous, even after the fluid had been filtered to remove all bacteria-sized organisms. Three years later, Peyton Rous identified one such factor, now named the Rous Sarcoma Virus. By the 1950s, many oncogenic viruses had been discovered and the RNA nature of these viruses had been established. In the 1960s, the reverse transcriptase enzyme was discovered. Finally, in 1981, the first human retrovirus was discovered, this being the Human T-cell Leukemia Virus (HTLV-1). The latter virus is a well-known tumor viruses.
There are two groups of RNA tumor viruses, the Oncovirinae and the Lentivirinae. Examples of the first group include the Rous Sarcoma Virus, HTLV-1, and HTLV-2 (which is also known as hairy cell leukemia virus). A prominent example of the second group is the Human Immunodeficiency Virus (HIV). A characteristic of HIV and other members of the second group is the long period of latency before symptoms of infection appear.
As for many viruses, the investigation of RNA tumor viruses involves growing the virus in a culture of whatever eukaryotic cell the virus is able to replicate inside. Then, the virus is purified. Subsequently, the virus can be studied using a variety of molecular and genetic techniques, and the electron microscope to assess the shape of the virus particles.
Some RNA tumor viruses never exist outside of the host cell, and lack an envelope around their genetic material. Viruses such as the mouse mammary tumor virus have an envelope that has spikes protruding from the surface. Other RNA tumor viruses contain spikes that are less prominent. Lentiviruses are an example of the latter shape.
The envelope of RNA tumor viruses comes from the membrane surrounding the host cell. The virus acquires this envelope as it emerges from the host cell. Within this envelope are distinctive proteins, which are coded for by the envelope, or env, gene. Another characteristic component of RNA tumor viruses is the presence of a protein that coats the viral RNA. The gag gene codes for this latter protein. The protein encoded by the gag gene is also found in the envelope. The presence of these two protein species in RNA tumor viruses is being explored as a target for therapy to prevent RNA virus-induced cancer.
Another hallmark of RNA tumor viruses is the presence of a gene that is designated pol. The products of the pol gene include reverse transcriptase, another enzyme that helps integrate the viral genetic material into the host genome, and other enzymes that help process the genetic material and viral proteins so as to permit assembly of new virus. These essential functions have made the pol gene the target of antiviral strategies.
The infection process begins with the binding of the virus particles to a specific molecule on the surface of the host cell. Generically, such molecules are termed receptors. Once the virus is bound, it can be taken into the host by the process of endocytosis. Blocking the viral recognition of the host receptor and binding of the virus is yet another strategy to prevent tumor development.
The molecular basis for the transformation of cells by RNA tumor viruses was revealed by a number of scientists, including the Nobel laureate Harold Varmus. He and the others demonstrated that the cancer genes (oncogenes) of the viruses were similar or the same as certain genes with the nucleic acid of the host cell. When a virus infects the host, the host gene may become part of a new virus particle following viral replication. Over time, the host gene may become altered in subsequent rounds of viral replication. Eventually, this altered host gene may end up replacing a normal gene in a new host cell. The altered gene produces a protein that is involved in over-riding the controls on the division process of the host cell. The result is the uncontrolled cell division that is the hallmark of a cancer cell.
See also AIDS, recent advances in research and treatment; Immunodeficiency; Viral genetics