Retrovirus-induced Immunodeficiency and Cancer

Abstract

Malignant disease represents a major complication of human immunodeficiency virus-1 (HIV)-induced immunodeficiency in the setting of AIDS. Three cancers have been identified as AIDS-defining conditions, including Kaposi’s sarcoma, non-Hodgkin’s lymphomas, and invasive cervical carcinoma. In addition, classical Hodgkin’s lymphoma, anal cancer, and other cancers are increased in incidence and/or severity in the context of HIV infection and AIDS. AIDS-associated malignancies may arise as a result of inadequate immune surveillance, insufficient or defective immune response, the reactivation of oncogenic viruses, and/or as a direct effect of HIV infection. In the developed world, the widespread use of highly active anti-retroviral therapy (HAART) has not uniformly reduced the incidence of AIDS-related cancers, which implicates a multifactorial etiology. Infection of the rhesus macaque (Macaca mulatta) with simian immunodeficiency virus (SIV) offers a faithful and reliable model of human AIDS and of AIDS-related non-Hodgkin’s lymphoma (AIDS-NHL). Like the human disease, lymphomas in SIV-infected macaques represent a clonal expansion of B-cell origin, which are widely disseminated in unusual anatomic sites and frequently infected with the simian homologue of Epstein-Barr virus. Resolution of the multifactorial etiology of AIDS-NHL may be possible through the use of this animal model and through analysis of interactions between viral co-infections, SIV genetic variation, genetic alterations, and other contributing factors.