Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL062235-02
Application #
6184619
Study Section
Special Emphasis Panel (ZHL1-CSR-G (F2))
Project Start
1999-04-12
Project End
2004-03-31
Budget Start
2000-04-01
Budget End
2001-03-31
Support Year
2
Fiscal Year
2000
Total Cost
$1,180,132
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Pathology
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Usadi, Benjamin; Bruhn, Roberta; Lin, Jue et al. (2016) Telomere Length, Proviral Load and Neurologic Impairment in HTLV-1 and HTLV-2-Infected Subjects. Viruses 8:
Guiltinan, Anne M; Kaidarova, Zhanna; Behan, Dee et al. (2013) Major depression and generalized anxiety disorder among human T-lymphotropic virus types I- and II-infected former blood donors. Transfusion 53:60-8
Murphy, Edward L (2013) Health outcomes in recipients of blood transfusion - observational studies versus randomized clinical trials. ISBT Sci Ser 8:172-176
Douceron, Estelle; Kaidarova, Zhanna; Miyazato, Paola et al. (2012) HTLV-2 APH-2 expression is correlated with proviral load but APH-2 does not promote lymphocytosis. J Infect Dis 205:82-6
Biswas, Hope H; Kaidarova, Zhanna; Garratty, George et al. (2010) Increased all-cause and cancer mortality in HTLV-II infection. J Acquir Immune Defic Syndr 54:290-6
Norris, Philip J; Hirschkorn, Dale F; DeVita, Deborah A et al. (2010) Human T cell leukemia virus type 1 infection drives spontaneous proliferation of natural killer cells. Virulence 1:19-28
Lam, Lynda; Engstrom, John (2010) Teaching video NeuroImages: the breathing arm: respiratory brachial synkinesis. Neurology 74:e69
Biswas, H H; Engstrom, J W; Kaidarova, Z et al. (2009) Neurologic abnormalities in HTLV-I- and HTLV-II-infected individuals without overt myelopathy. Neurology 73:781-9
Ndhlovu, L C; Snyder-Cappione, J E; Carvalho, K I et al. (2009) Lower numbers of circulating Natural Killer T (NK T) cells in individuals with human T lymphotropic virus type 1 (HTLV-1) associated neurological disease. Clin Exp Immunol 158:294-9
DeVita, Deborah A; White, Mary C; Zhao, Xin et al. (2009) Determinants of subject visit participation in a prospective cohort study of HTLV infection. BMC Med Res Methodol 9:19

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