HTLV-1 infection cause abnormalities in the immunological response characterized by spontaneous T cell proliferation and production of high levels of pro-inflammatory (IFN-gamma and TNF-alpha) cytokines. The myelopathy associated to HTLV-1 (HAM/TSP) and acute T cell leukemia are the most important diseases related to HTLV-1 and the pathogenesis of these diseases are associated with abnormalities in the T cell response. However while abnormalities in T cell responses are found in a large percentage of individuals infected with HTLV-1, HAM/TSP is documented in less than 5% of the infected individuals. The major hypothesis of this application is that clinical, neurological and immunological abnormalities occur in higher frequency than previously described in HTLV-1 infected patients. The major aim of this application is to identify early, clinical and immunological markers of disease in HTLV-1 infected individuals.
The aim 1 is to identify clinical manifestations associated to HTLV-I. This will be performed analyzing the clinical data that has been generated in the last 5 years and compared with blood donors not infected with HTLV-1 in a case control study.
The aim 2 will determine by sophisticated complementary exams if HTLV-1 carriers who have immunological abnormalities similar to that observed in HAM/TSP will have early evidence of neurological involvement. This will be tested in a case control study comparing the neurological findings, cytokine levels in cerebral spinal fluid and magnetic resonance imaging in HTLV-1 carriers who have high levels of IFN-gamma and lack of modulation of IFN-gamma production, similar to that observed in HAM/TSP, with HTLV-1 carriers who have no or mild alterations in their immunological responses. Results of these studies will contribute to identify clinical and neurological manifestations associated with HTLV-1, which can be confirmed in the future by a longitudinal study in the natural history of disease and will shed light on future more effective and earlier therapeutic interventions to this disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Research Grants (R03)
Project #
5R03AI060830-02
Application #
7089857
Study Section
Special Emphasis Panel (ZRG1-IDM-G (02))
Program Officer
Dempsey, Walla L
Project Start
2005-07-01
Project End
2007-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
2
Fiscal Year
2006
Total Cost
$52,731
Indirect Cost
Name
Federal University of Bahia
Department
Type
DUNS #
900845397
City
Salvador
State
Country
Brazil
Zip Code
40110-160
Caskey, Marina F; Morgan, Daniel J; Porto, Aurelia F et al. (2007) Clinical manifestations associated with HTLV type I infection: a cross-sectional study. AIDS Res Hum Retroviruses 23:365-71
Morgan, Daniel J; Caskey, Marina F; Abbehusen, Cristiane et al. (2007) Brain magnetic resonance imaging white matter lesions are frequent in HTLV-I carriers and do not discriminate from HAM/TSP. AIDS Res Hum Retroviruses 23:1499-504
Santos, Silvane B; Porto, Aurelia F; Muniz, Andre Luiz et al. (2006) Modulation of T cell responses in HTLV-1 carriers and in patients with myelopathy associated with HTLV-1. Neuroimmunomodulation 13:145-51
Guerreiro, J B; Santos, S B; Morgan, D J et al. (2006) Levels of serum chemokines discriminate clinical myelopathy associated with human T lymphotropic virus type 1 (HTLV-1)/tropical spastic paraparesis (HAM/TSP) disease from HTLV-1 carrier state. Clin Exp Immunol 145:296-301