Micro - 4th Asessment - Human Lymphotropic Viruses - 3 Feb 2006

Human T-Cell Lymphotropic Viruses

Fourth Medical, 2007 Prof. Widad Al-Nakib, FRCPath.

Introduction • Human T-cell leukemia virus type I (HTLV-I),was isolated from patients with adult T-cell leukemia (ATL) in Japan. • Subsequent work by Gessain associated the virus with spastic paraparesis, a neurological disorder that is also called HTLV-I–associated myelopathy (HAM). • Thus, HTLV-I has TWO associated diseases.

Human T-cell Leukemia Virus Type II • In 1982, Kalyanaraman identified the HTLV-II virus in cell lines from a patient with atypical hairy cell leukemia (HCL), the first disease thought to be associated with the virus. • Another hematologic disorder linked with HTLV-II is large granular lymphocytic leukemia (LGL), as discovered by Loughran in 1992; however, a subsequent study by Martin in 1993 showed no HTLV-II virus within the relevant cells of a patient with large granular lymphocytosis, which often leads to a tentative diagnosis of LGL.

Pathophysiology • HTLV-I and II are transmitted from mother to child via breast feeding or childbirth • Through sexual contact • Through blood contact, either by transfusion or by reuse of injection equipment

Human T-cell Leukemia Virus Type I • HTLV-I is the etiologic agent for ATL and HAM. • In ATL, a proliferative disorder of T cells is observed, characterized by skin lesions, lymphadenopathy, hepatosplenomegaly, lytic bone lesions, and hypercalcemia. • HAM, also called tropical spastic paraparesis (TSP), is a chronic progressive demyelinating disease that affects the spinal cord and white matter of the central nervous system, causing weakness and spasticity, predominately in the lower limbs.

Human T-cell leukemia virus type I • Major pathological findings: • Include inflammatory perivascular and parenchymal infiltration with degeneration. • Immunologic mechanism may be involved in the development of HAM. • Ocular complications are observed in both HAM and ATL.

Laboratory Diagnosis • HTLV-I and II infection is detected with enzymelinked immunosorbent assay (ELISA) and confirmed with Western blot. • Polymerase chain reaction (PCR) or enzyme immunoassays using virus-specific synthetic peptides are necessary to distinguish between types I and II. • Histologic Findings: ATL peripheral blood lymphocytes are found to have convoluted nuclei ("clover leaf" or "flower" lymphocytes).

Prevention • No proven HTLV-I or II prevention strategies are available, although transmission by blood transfusion can be prevented with blood donor screening for HTLV-I and HTLV-II. • Helpful measures include avoidance of shared injection equipment among IDUs (HTLV-II) and use of condoms (HTLVI).

Treatment • No cure or vaccine exists for HTLV-I or HTLVII. • ATL is treatable with chemotherapy. • Complete remission can occur, but relapse is common. • Patients who do not respond to chemotherapy, which often occurs, reportedly respond to interferon plus zidovudine or monoclonal antibodies, with limited success. • HAM treatment options are limited. Corticosteroids, plasmapheresis, cyclophosphamide, and interferon occasionally produce temporary improvement in signs and symptoms associated with HAM.