PATHOPHYSIOLOGY OF HTLV1 AND HTLVII INFECTION

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Despite an estimated 1 million cases of human T-lymphotropic virus type I (HTLV-I) infection worldwide, and over 174,000 cases of infection with HTLV-II in the United States, the clinical outcomes and pathogenesis of HTLV-I and -II infection are not well defined. Recent data from the NHLBI-sponsored Retrovirus Epidemiology Donor Study (REDS) HTLV Cohort Study and the literature suggest that HTLV-II predisposes to other infectious disease, and that it may cause a myelopathy similar to HTLV-I associated myelopathy (HAM). HTLV-I also causes adult T-cell leukemia (ATL), but it is controversial whether it increases the rate of other malignancies. Finally, there are reports that HTLV-I and/or HTLV-II are associated with immunologic syndromes including arthritis, uveitis and iritis; however, these associations have not been proven. This Project will test the following hypotheses derived from the literature and our own preliminary data: 1. Infection with HTLV-II, and to a lesser degree HTLV-I, predisposes to other infectious diseases. 2. HTLV-II causes myelopathy similar to HTLV-I associated myelopathy (HAM). 3. HTLV-I is associated with an increased risk of ATL and other malignancies. 4. Autoimmune conditions (e.g. arthritis and uveitis) are more common among HTLV-I and -II infected persons. We shall test these hypotheses during additional prospective investigation of the REDS cohort of 154 HTLV-I, 387 HTLV-II and 799 stratum matched seronegative former blood donors enrolled in 1990-92. Four follow-up visits of this cohort will have been completed through 1998 under funding by the initial NHLBI REDS contracts. This application proposes two additional biennial visits from 1999 through 2004, including structured health interviews, selected physical examinations, medical record review and targeted diagnostic work-ups. Blood will be collected from all subjects at each visit for complete blood counts, measurement of HTLV viral load, and for an extensive specimen repository.