Simian models of acquired immunodeficiency syndrome (AIDS): a review.

Abstract

Reports of the unprecedented occurrence of Kaposi’s sarcoma and fatal Pneumocystis carinii pneumonia in previously healthy homosexual men in New York and California in 198 1 heralded the onset of the current human epidemic known as the acquired immunodeficiency syndrome Since those initial reports, the incidence and spread of this disease have increased dramatically. Individuals affected with AIDS develop a prodrome of generalized lymphadenopathy, referred to as lymphadenopathy syndrome, frequently culminating in a selective and profound depression of cellmediated immunity that thus far appears irreversible. Typically, this immunodeficiency is characterized by a reversal of the ratio of T4 + (helper-inducer) to T8 + (suppressor-cytotoxic) subsets of lymphocytes in the peripheral circulation, impairment of delayed cutaneous hypersensitivity and decreased responsiveness of T-lymphocytes to in vitro mitogen stimulation. Patients with AIDS frequently develop life-threatening infections with one or more of the following opportunistic pathogens: Pneumocystis carinii, Cryptococcus neoformans, Toxoplasma gondii, Candida albicans, Mycobacterium tuberculosis, Mycobacterium aviumintracellulare, cytomegalovirus (CMV), Herpesvirus hominis (simplex), adenoviruses and papovaviruses. In addition, Kaposi’s sarcoma and Burkitt’s-like lymphoma occur with much greater frequency in AIDS patients than in the general population. Although initially confined to certain high-risk groups that included promiscuous male homosexuals, intravenous drug-abusers, Haitians, hemophiliacs, and blood transfusion receipients, AIDS is being increasingly recognized in patients that do not belong to any of these groups. It is now well established that the disease can be transmitted through both homosexual and heterosexual contact through use of contaminated hypodermic needles and blood products, and from infected mothers to their newborn children. Early epidemiologic evidence strongly suggested that AIDS was caused by a transmissible agent. In 1983, a retrovirus variously termed lymphadenopathy-associated virus (LAV), human T-lymphotropic virus type I11 (HTLV111) or AIDS-associated retrovirus (ARV) was isolated and shown to be the cause of AIDS.2,39,45 This agent will be referred to as HTLV-III/LAV in this review. Interestingly, HTLV-III/LAV has been shown to have a number of biological characteristics in common with several viruses of ungulates classified in the lentivirus subfamily of retroviruse~.~~~ ~~ These agents include maedi-visna virus (MVV), caprine arthritis-encephalitis virus (CAEV) and equine infectious anemia virus (EIAV). Recently, HTLV-III/LAV has been shown to be neuropathic and associated with dementia and a characteristic granulomatous encephalitis in adult as well as pediatric patients.