Despite an estimated 1 million case of human T-lymphotropic virus type I (HTLV-I) infection worldwide, and over 197,000 cases of infection with HTLV-II in the United States, the clinical outcomes and pathogenesis of HTLV-I and -II infection are still not well defined. Data from the previous funding period of this HTLV Outcomes Study (HOST) indicate that HTLV-II predisposes to pneumonia, bronchitis and arthritis, causes a myelopathy similar to HTLV-I associated myelopathy (HAM), and is associated with increased all-cause mortality. HTLV-I has previously been associated with adult T-cell leukemia (ATL), HAM and arthritis, uveitis and iritis. These pulmonary, neurologic and immunologic syndromes have not been well characterized clinically or biologically, especially for HTLV-II. This Competing Continuation Project will test the following hypotheses: 1. Infection with HTLV-II, and to a lesser degree HTLV-I, predisposes to pneumonia and bronchitis because of HTLV-induced, immune-mediated pulmonary damage. 2. HTLV-II causes myelopathy resembling HTLV-I associated myelopathy (HAM) via similar mechanisms immune-mediated neurotoxicity. 3. HTLV-II, and perhaps HTLV-I, is associated with increased mortality, perhaps due to a higher death rate from malignant and/or cardiovascular causes. 4. HTLV-I and -II are associated with a higher incidence of arthritis and other autoimmune conditions. We shall test these hypotheses during additional prospective investigation of the HOST cohort of 154 HTLVI, 387 HTLV-II and 799 stratum matched seronegative former blood donors enrolled in 1990-92. 6 biennial visits of this cohort have been completed to date. This application proposes 2 additional visits from 2005 through 2009, including structured health interviews, screening physical examinations, medical record review and targeted physician diagnostic work-ups. Blood will be collected from all subjects, and bronchoalveolar lavage fluid and cerebrospinal fluid from subsets with disease, for studies of HTLV virology and immunology.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL062235-08
Application #
7178460
Study Section
Special Emphasis Panel (ZRG1-HOP-N (90))
Program Officer
Barbosa, Luiz H
Project Start
1999-04-12
Project End
2009-01-31
Budget Start
2007-02-01
Budget End
2008-01-31
Support Year
8
Fiscal Year
2007
Total Cost
$923,015
Indirect Cost
Name
University of California San Francisco
Department
Pathology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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