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Retroviruses Associated with Leukemia and Ablative Syndromes in Animals and in Human Beings¹

Department of Cancer Biology, Harvard University School of Public Health, Boston, Massachusetts 02115

T-lymphotropic retroviruses of cats cause lymphopenia and immunosuppression and represent the major cause of death in that species. Similarly HTLV-I which is T4 tropic is associated with an increased risk for development of infectious disease in regions where the virus is endemic. Since HTLV-I is also believed to be transmitted by blood and by sexual intercourse we considered the possibility that a variant form of HTLV might cause AIDS. The identification of cross-reactive antibodies to HTLV-I-MA in a third or more of the AIDS patients and in suspicious blood donors that donated to transfusion-associated cases of AIDS eventually led to the recognition of HTLV-III, the causative agent of AIDS.

The protein most associated with lymphocyte immortalization or transformation in the case of HTLV-I is p42. The proteins of HTLV-I encoded by the amino terminus of the env gene designated gp61 and gp45 are the most immunogenic antigens of this virus. Similarly those encoded by the amino terminus of the env gene HTLV-III designated gp160 and gp120 appear to be the most immunogenic markers for this agent. Almost all AIDS patients, ARC patients, and asymptomatic hemophiliacs have detectable antibodies to gp120 and gp160.

HTLV-III related agents designated STLV-III have been found in macaque monkeys that develop simian AIDS and high prevalence rates of antibodies to STLV-III can be found in healthy African green monkeys. We hypothesize that the STLV-III of African green monkeys could represent a recent source of the virus to have infected humans in central Africa where the human epidemic probably began. The recognition that up to one million people may already be infected with HTLV-III in the United States alone indicates the need for development of a vaccine. The availability of primate species infected with the serologically related STLV-III agents that either resist disease development (African green monkeys) or succumb to an AIDS-type syndrome (rhesus) provide models that should aid in our attempts to develop such vaccines.