Abstract
BackgroundHuman T cell lymphotropic virus type 1 (HTLV-1) infection can lead to development of adult T cell leukemia/lymphoma (ATL) or HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in a subset of infected subjects. HTLV-1 basic leucine zipper factor (HBZ) gene has a critical role in HTLV-1 infectivity and the development of ATL and HAM/TSP. However, little is known about the immune response against HBZ in HTLV-1-infected individuals. In this study, we examined antibody responses against HBZ in serum/plasma samples from 436 subjects including HTLV-1 seronegative donors, asymptomatic carriers (AC), ATL, and HAM/TSP patients using the luciferase immunoprecipitation system.ResultsImmunoreactivity against HBZ was detected in subsets of all HTLV-1-infected individuals but the test did not discriminate between AC, ATL and HAM/TSP. However, the frequency of detection of HBZ-specific antibodies in the serum of ATL patients with the chronic subtype was higher than in ATL patients with the lymphomatous subtype. Antibody responses against HBZ were also detected in cerebrospinal fluid of HAM/TSP patients with anti-HBZ in serum. Antibody responses against HBZ did not correlate with proviral load and HBZ mRNA expression in HAM/TSP patients, but the presence of an HBZ-specific response was associated with reduced CD4+ T cell activation in HAM/TSP patients. Moreover, HBZ-specific antibody inhibited lymphoproliferation in the PBMC of HAM/TSP patients.ConclusionsThis is the first report demonstrating humoral immune response against HBZ associated with HTLV-I infection. Thus, a humoral immune response against HBZ might play a role in HTLV-1 infection.
Highlights
Human T cell lymphotropic virus type 1 (HTLV-1) infection can lead to development of adult T cell leukemia/lymphoma (ATL) or HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in a subset of infected subjects
Since these findings suggested that HTLV-1 basic leucine zipper factor (HBZ) has a critical role in HTLV-1 persistence and the development of ATL and HAM/TSP, it is important to define HBZ-specific immune responses in HTLV-1-infected individuals
Antibody responses against HBZ in cerebrospinal fluid (CSF) Since strong antibody responses against HTLV-1 antigens have been reported in both serum and CSF of HAM/TSP patients [10,32], we examined antibody responses for HTLV-1 Gag, Env, Tax and HBZ in both serum and CSF samples of HAM/TSP patients with or without HBZ-specific antibody responses
Summary
Human T cell lymphotropic virus type 1 (HTLV-1) infection can lead to development of adult T cell leukemia/lymphoma (ATL) or HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in a subset of infected subjects. HTLV-1 basic leucine zipper factor (HBZ) gene has a critical role in HTLV-1 infectivity and the development of ATL and HAM/TSP. While the majority of infected individuals are asymptomatic carriers (AC) of the virus, 5-10% of infected people develop either adult T cell leukemia/lymphoma (ATL) [2] or a chronic, progressive, neurological disease termed HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) [3,4]. HBZ mRNA expression was detected in HAM/TSP patients, and was correlated with proviral load and disease severity [27] Since these findings suggested that HBZ has a critical role in HTLV-1 persistence and the development of ATL and HAM/TSP, it is important to define HBZ-specific immune responses in HTLV-1-infected individuals
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