ABSTRACT
Exogenous human retroviruses 99 Human T cell leukemia virus-1 100 Epidemiology and transmission 100 Adult T cell leukemia/lymphoma 102 Other human T cell leukemia virus-1-associated diseases 102 Prevention 103 Human immunodeficiency virus types 1 and 2 103 Epidemiology and transmission 103 Immunosuppression and non-Hodgkin lymphoma 105 Human immunodeficiency virus-associated non-Hodgkin 106
lymphoma Antiviral therapy and lymphoma 107 Human immunodeficiency virus-associated non-Hodgkin 108
lymphoma in Africa
Hematologic cancers and human immunodeficiency virus 109 infection among children
Human immunodeficiency virus 2 and non-Hodgkin 109 lymphoma
Hodgkin disease and HIV infection 109 Other human immunodeficiency virus-associated 109
malignancies Prevention of human immunodeficiency virus-associated 110
lymphoma Key points 110 References 111
Exogenous retroviruses are distinguished by a RNA genome which replicates through the action of the enzyme reverse transcriptase, via a DNA intermediate that integrates into the host chromosomal DNA. They are among the first known viruses, although until the late 1970s and early 1980s, they had only been found in animals, usually in association with neoplastic disease. In 1908, Ellerman and Bang first demonstrated the transmission of leukemia among chickens by ‘an agent that passed through a filter’. However, leukemia was not recognized as a malignant disease until the 1930s. It was Peyton Rous in 1911 who first demonstrated the acellular transmission of a solid tumor (sarcoma) between chickens (the term virus had not yet been coined). Although both conditions are now known to be caused by retroviruses, the research community was not receptive to the notion that a chronic disease may have an infectious cause and it was to be 55 years before Rous received the Nobel Prize for his seminal discovery. In 1936, Bittner demonstrated that predisposition to breast cancer
subsequently found to be the retrovirus mouse mammary tumor virus. In 1951 Gross discovered the first murine leukemia virus. Many other retroviruses have since been identified including the avian leukosis and bovine leukemia viruses. The first human retrovirus (human T cell leukemia virus [HTLV-1]) was identified by Gallo and colleagues in 1979 and the findings were published in 1980.1 Three other retroviruses were subsequently identified – HTLV-2, and the human immunodeficiency viruses types 1 and 2. Although HTLV-2 was identified in a person with hairy cell leukemia, it has not been firmly linked with any human disease, while HTLV-1 and human immunodeficiency virus (HIV)-1 and 2 are important causes of morbidity and mortality. In addition to other malignant and nonmalignant diseases, in the year 2002, together these three viruses have been estimated to account for up to 40 000 cases of hematologic malignancy – more than any other known cause (Table 6.1).2,3 The human retroviruses target cells of the immune system, particularly mature CD4 T cells, impair their function and cause them either to grow abnormally (HTLV-1), or to die (HIV-1 and HIV-2).
