The below mentioned article provides a note on oncogenic virus.
Onkos in Greek means a mass or a tumour. Several types of cancer is now known to be caused by viruses. These viruses which include both DNA and RNA animal viruses are called oncogenic. Cancer is a disease characterized by uncontrolled cell multiplication resulting in the formation of a malignant tumour.
A tumour is called benign when it remains localized as a compact mass being surrounded by the connective tissues of the host. Such tumour is harmless. A tumour becomes malignant when it spreads through the circulatory system to other parts of the body and forms new tumours by a process called metastasis. Such tumour is then turned into a cancer.
Cancer cells differ from normal cells in many ways. Among these are higher rates of mitosis, abnormal chromosome number, higher frequency of chromosomal aberration. But more important characteristics of cancer cells are that they are dedifferentiated and they fail to exhibit contact inhibition.
Dedifferentiation means that a differentiated cell — once it becomes a cancer cell — reverts to its original form and behaves like an embryonic cell. It starts dividing producing many cancer cells. Contact-inhibition is a phenomenon exhibited by normal cells. When normal cells are grown in culture, they require a firm attachment to a substratum for growth i.e. they are adherent.
When growing cells come into contact with each other, their growth stops. As a result, normal cells grow as a monolayer in a culture. In contrast, cancer cells are non-adherent and they grow in multilayers, because growth continues even if the cells come in contact. The cancer cells do not adhere to each other tightly. So they can be dislodged and carried to other parts of the body.
Depending on the tissue of origin, cancers are classified as carcinoma if they develop in the epithelial tissues, as sarcoma if they originate from the connective tissues, as leukaemia when leucocytes are affected, and lymphoma when the lymph nodes and spleen are affected.
Normally, cell division in an adult person is a highly regulated process and the body maintains a steady-state by balancing cell birth and cell death. Some tissues like blood require constant replenishment of new cells, because of high death-rate of blood cells. Occasionally, the regulation of new cell formation by mitosis may break down and a cell starts dividing at a rapid rate producing a clone of unwanted cells resulting in the formation of a tumour.
Among several factors that cause transformation of normal cell into a malignant tumour cell (cancer cell) are also some viruses which are commonly called tumour viruses. The other factors which are more common in causing cancer are a large variety of chemicals and radiations. All the factors that can cause cancer bring about an alteration in the genetic material. The chemical agents and radiations which have the potentiality to cause cancer are carcinogens.
The connection between virus and cancer was shown for the first time by Peyton Rous in 1911 when he proved that chicken sarcoma could be transmitted to healthy chicken. The causative agent is known as Rous Sarcoma Virus (RSV). It is a retrovirus having a single-stranded RNA genome which replicates like other retroviruses through a double-stranded DNA intermediate.
The latter is integrated into a host chromosome and becomes a provirus. All oncogenic viruses that have been discovered till now possess this characteristic i.e. their genetic material is integrated into the host cell DNA and it replicates along with the host cell chromosome. About 10% of cancers are now known to be of viral origin.
DNA Oncogenic Viruses:
Oncogenic viruses are distributed in several families of DNA viruses. These include Herpesviridae, Poxviridae, Papovaviridae and Hepadnaviridae. The Herpesviridae include the Epstein-Barr Virus (EBV) which has been found as the cause of two forms of human cancers — Burkitt’s lymphoma and nasopharyngeal carcinoma. EBV has also been implicated with Hodgkin’s disease, a cancer of lymphatic system. Other herpes-viruses have been associated with human cancers of lip and cervix.
The Papilloma viruses belonging to the Papovaviridae cause benign tumours as well as cancer in several species including human. In humans, papilloma viruses cause uterine (cervical) cancer. Another member of Papovaviridae, the Simian Virus 40 (SV40) is among the best studied DNA tumour viruses.
Natural host of SV 40 is cultured fibroblast cells of monkey. Such a cell culture is called permissive, because it allows viral multiplication and release of progeny viruses by cell lysis. On the other hand, when SV 40 is inoculated into non-permissive cell cultures e.g. the fibroblast cells of mice, the virus cannot multiply, but in a small number cells the viral DNA is, integrated with the host DNA causing their transformation into cancer cells.
Due to integration into the host chromosome viral multiplication and cell lysis are absent. The phenomenon is comparable to lysogeny observed in temperate phage infection of bacteria. Integration of some DNA viruses is site-specific i.e. the viral DNA is inserted into a host chromosome at a specific site. But papova-viruses do not have such specificity and can be inserted at random.
Hepatitis B virus (HBV) belonging to the Hepadnaviridae causes cancer of liver. Many animal experiments have yielded results which clearly indicate a connection of HBV and liver cancer. Although direct proof is lacking in case of human beings, a survey revealed that all people with liver cancer had a previous infection of HBV.
RNA Oncogenic Viruses:
Among the RNA viruses only some members of the family Retro-viridae can cause cancer. Other RNA viruses which replicate by RNA replicase are non-oncogenic. Retroviruses which have a single- stranded RNA genome replicate via a double-stranded DNA produced by an RNA-dependent DNA polymerase (reverse transcriptase) and they insert the DNA copy into the host chromosome as a provirus.
Rous Sarcoma Virus (RSV) is of historical importance, because it was the first tumour-inducing virus to be studied. RSV is a retrovirus with a single-stranded RNA genome and its DNA copy is integrated into a specific site of the host chromosome as a provirus.
Research on RSV revealed identification of a cancer-inducing gene (an oncogene) in RSV genome. This gene, called src, is not essential for viral replication, as it does not code for any viral proteins. Later, it was discovered that a copy of the src gene is present in the host chromosome of normal cells and it was not oncogenic.
Thus, the viral src gene which is oncogenic is derived from the host. How the non-oncogenic chromosomal src gene is converted to an oncogene in RSV is not clearly understood. It may occur through a mutation. The entry of a chromosomal gene into the viral genome possibly occurs through a process similar to that which operates in restricted transduction in bacteria.
It is thought that the RSV DNA produced through reverse transcription is inserted next to the chromosomal src gene and during transcription of the RSV RNA genome, src gene might be included. In this way, src gene might enter into the viral genome. RSV causes cancer in chicken.
Similar retroviruses are known to cause cancer in other animals including monkey. But definite evidence of retroviruses causing cancer in humans was not available until 1980. In that year Gallo isolated a virus that could transform normal T-lymphocytes into cancerous T-lymphocytes causing a disease, called T-cell leukaemia.
The virus is known as Human T-cell Leukaemia Virus (HTLV). Later research during 1990s has confirmed the role of HTLV in causing human leukaemia. Another HTLV was later discovered causing hairy cell leukaemia in man.
The malignant leucocytes develop hairy outgrowths on their surface. The second virus has been designated as HTLV-II. These retroviruses have been shown to transform normal T-cells by a regulatory protein which stimulates uncontrolled cell division. Besides leukaemia, HTLV is also known to cause neurological disorders, like spastic para-paresis. T-cell leukaemia is more or less restricted in several countries, like Japan, West Indies and some parts of West Africa.