Retroviruses and human cancer

Molecular biology of retroviral infections

a. After infecting the cell, all retroviruses are reverse-transcribed into provirus DNA, which is incorporated randomly into the host genome (DNA).

b. Replication competent provirus DNA is transcribed into RNA, which is subsequently translated into viral proteins. The RNA and some viral proteins form new retroviruses that leave the cell, take some of the membrane along as their envelope, and then infect other cells.

c. Some retroviruses, such as human T cell lymphotropic virus type 1 (HTLV-1), transform cells by being inserted next to normal cellular oncogenes. These c-onc become abnormally activated. Such retroviruses do not have oncogenes themselves, and malignant transformation is a slow process.

d. Viral DNA can also combine with DNA of a normal cell gene and make new retroviruses that contain RNA copies of a normal host gene. If the normal host gene is a cellular oncogene (proto-oncogene or c-onc), the new virus can insert the oncogene into ectopic locations in the cell genome of newly infected cells and cause malignant transformation. Some of these viruses lose their own genes when they combine with host DNA and become replication deficient.

2. Nomenclature of retroviral oncogenes is usually based on the name of the animal tumor from which the retrovirus is extracted. Examples include src --Rous s a rc oma virus of chickens (the first oncovirus discovered); sis -- si mian s arcoma virus; erb -- er ythro b lastosis virus of chickens; H-ras -- H arvey ra t s arcoma virus; K-ras -- K irsten ra t s arcoma virus; myc -- my elo c ytoma; ras -- ra t s arcoma.

a. Human T cell lymphotropic virus type 1 (HTLV-1) causes lymphoblastic leukemia in southern Japan and other countries. It is the only virus to date that has been clearly shown to cause a human cancer. HTLV-1 is a replication competent virus that does not possess an oncogene. Part of its transforming activity occurs by insertional mutagenesis. It also codes for the TAX protein, which induces infected lymphocytes to produce interleukin-2 receptor proteins. Interleukin-2 attaches to these receptors and stimulates infected cells to proliferate. Other unclear events are necessary, however, for leukemia to develop, and only a very small percentage of infected persons develop leukemia.

b. HTLV-2 may be causal for a small percentage of hairy cell leukemias and a variety of T cell lymphoproliferative disorders.

c. HTLV-3 (human immunodeficiency virus [HIV]) is associated with aggressive B lymphocyte malignancies in patients with AIDS. It also produces the TAT protein, which stimulates proliferation of Kaposi’s sarcoma cells. These cells are not infected by the virus.

Дата добавления: 2015-06-04