Human T lymphotropic virus type I (HTLV-I) is associated with a chronic progressive neurological disorder known as HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a disease clinically similar to the chronic progressive form of multiple sclerosis (MS). Other viruses such as human herpes virus type 6 (HHV-6) have been associated with MS. An understanding of the pathogenesis of a neurologic disease with a known viral etiology will aid in defining similar mechanisms of pathogenesis in MS, a disease of unknown etiology.

Areas of research addressing these neurovirological and neuroimmunological issues include:
o The host immune response in HAM/TSP, particularly the role of CD8+, HTLV-I-Tax protein-specific cytotoxic T lymphocytes (CTL).
o The detection of these immunopathogenic CTL as well as the localization of human retroviral sequences in the central nervous system of HAM/TSP patients.
o Association of HHV-6 and MS.
o Development of immunotherapeutic strategies for the treatment of HAM/TSP, including a clinical trial of B-IFN therapy.
Major findings include:
o The demonstration of spontaneous proliferation of CD4+ and CD8+ cells from HAM/TSP patients ex vivo, including Tax-specific CD8+ CTL directly isolated from PBL of HAM/TSP patients.
o The quantitation of HTLV-I DNA in PBL of HAM/TSP patients by real-time Taqman PCR.
o Identification of altered peptide ligands that have been shown to interfere specifically with antigen-specific CTL clones.
o Association of HHV-6 and MS based on increased IgM response to HHV-6 early antigen, detection of HHV-6 DNA in sera from MS patients, and the observation of an increased proliferative response to the HHV-6A variant in MS patients.
Collectively, these results continue to define the role of human viruses in chronic progressive neurologic disease.

Selected Publications: