Human retroviruses after 20 years: a perspective from the past and prospects for their future control

Among viruses the human retroviruses may be of special interest to immunologists, because they target cells of the immune system, particularly mature CD4+ T cells, impair their function and cause them to grow abnormally (human T-cell leukemia virus, HTLV) or to die (human immunodeficiency virus, HIV). Human retroviruses cause disease ranging from neurological disorders and leukemias (HTLV-1) to AIDS (acquired immunodeficiency virus) (HIV) and promote development of several types of malignancies (HIV). They share many common features, but their contrasts are greater, especially the far greater replication and variation of HIV associated with its greater genomic complexity. Both have evolved striking redundancy for mechanisms which promote their survival. Thus, HTLV has redundant mechanisms for promoting growth of provirus containing T cells needed for virus continuity, because it is chiefly through its cellular DNA provirus that HTLV replicates and not through production of virions. Conversely, HIV has redundancy in its mechanisms for promoting virion replication and escape from the host immune system. It is via these redundant mechanisms that they produce disease: leukemias from mechanisms promoting T-cell proliferation (HTLV-1) and AIDS from mechanisms promoting virus replication and T-cell death (HIV). The practical challenges for the future are clear. For HTLV-1, education and control of breastfeeding. For HIV, the formidable tasks now ahead in part demand new kinds of talent, talents that will foster greater insights into the development of therapy for the developing countries, new forms of less toxic therapies for all infected persons, a continued and expanded commitment to education, and a persistent 'never say die' commitment to the development of a truly preventive vaccine with all the scientific and nonscientific challenges that these objectives face.