Human T-lymphotropic Virus Type I (HTLV-I) Proviral Load and Clinical Features in Iranian HAM/TSP Patients: Comparison of HTLV-I Proviral Load in HAM/TSP Patients.

Abstract

Human T-cell lymphotropic virus type I (HTLV-I) was the first human retrovirus discovered (1), and it has been estimated that 10-20 million people worldwide are infected with HTLV-I (2). This virus is endemic in several regions of the world, such as southwestern Japan, the Caribbean basin, Central Africa, South America, the Melanesian Islands, and the Middle East (3, 4). The prevalence of HTLV-I infection in Iran (Mashhad) is estimated to be 2-3% of the entire population, and 0.7% among blood donors (5). Most of HTLV-I-infected individuals remain asymptomatic carriers (6). Whereas, small percentage of infected individuals develop the neoplastic disease adult T-cell leukemia (ATL), and the inflammatory condition HTLV-I- associated myelopathy/tropical spastic paraparesis (HAM/TSP) (7). Only 5% of HTLV-I infected people develop HAM/TSP (8). HAM/TSP results in demyelination of the spinal cord and clinical manifestations of this disease include progressive muscle weakness and hyperreflexia of the lower limbs, sensory disturbance, urinary incontinence, and impotence (9-11). These symptoms are generally slowly progressive, while patients at older ages of onset show faster progression. Women are affected more frequently than men (12, 13). The precise pathophysiology of HAM/TSP is not yet clear but, previous studies suggested that both HTLV-I subgroups, host genetic and immunological factors may be associated with the development of HAM/TSP, particularly cytokine gene polymorphisms (14, 15). Proviral load is a major determinant of outcome for chronic virus infections such as HIV-1 and 2, hepatitis B virus, and hepatitis C virus. Also recent studies have suggested the important role of proviral load in the outcome of human T-lymphotropic virus-I infection (16). In patients with HAM/TSP, significantly higher proviral loads have been observed compared to asymptomatic carriers, suggesting that active HTLV-I viral replication plays a key role in the development of this disease. A recent study has shown that a high level of Tax expression and low CD8+ anti-viral efficiency are correlated with high proviral load (PVL) and HAM/TSP development (17). In a previous study the proviral load and host genetic risk factors for development of HAM/TSP between Iranian and Japanese HTLV-I infected individuals were compared, and it was found that the median HTLV-I proviral load of Iranian HAM/TSP patients was two-fold greater in HAM/TSP patients than in healthy carriers (HCs), whereas that of Japanese HAM/TSP patients was 13-fold greater than in HCs. In addition, The HTLV-I proviral load in Iranian HCs was significantly higher than Japanese HCs. These significant differences of proviral load between two populations reflect the role of genetic factors such as the human leukocyte antigen (HLA) genotype in populations. In this study the Iranian genome DNA samples were extracted from the whole blood but Japanese samples were from the peripheral blood mononuclear cells (PBMCs). The Iranian proviral load was probably underestimated in comparison with Japanese ones (18). The aim of this study was to evaluate the proviral load and clinical manifestation of HAM/TSP among Iranian to compare with other endemic parts of the world.