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Humoral immune response to HTLV-1 basic leucine zipper factor (HBZ) in HTLV-1-infected individuals.

Enose-Akahata Y, Abrams A, Massoud R, Bialuk I, Johnson KR, Green PL, Maloney EM, Jacobson S - Retrovirology (2013)

Bottom Line: Immunoreactivity against HBZ was detected in subsets of all HTLV-1-infected individuals but the test did not discriminate between AC, ATL and HAM/TSP.This 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.

ABSTRACT

Background: 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. 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.

Results: Immunoreactivity 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.

Conclusions: This 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.

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Detection of antibody responses against HTLV-1 in serum and CSF of HAM/TSP patients. The data were obtained from 5 HAM/TSP patients including 2 patients (#1 and #2) and 3 patients (#5, #6 and #7) with and without HBZ-specific antibody response, respectively. Antibody responses for Gag (A), Env (B), Tax (C) and HBZ (D) were examined in serum (opened bar) and in CSF (closed bar). (E) Ratio of immunoreactivities against HTLV-1 Gag, Env, Tax and HBZ in CSF to those in serum of two HAM/TSP patients with HBZ-specific antibody responses.
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Figure 3: Detection of antibody responses against HTLV-1 in serum and CSF of HAM/TSP patients. The data were obtained from 5 HAM/TSP patients including 2 patients (#1 and #2) and 3 patients (#5, #6 and #7) with and without HBZ-specific antibody response, respectively. Antibody responses for Gag (A), Env (B), Tax (C) and HBZ (D) were examined in serum (opened bar) and in CSF (closed bar). (E) Ratio of immunoreactivities against HTLV-1 Gag, Env, Tax and HBZ in CSF to those in serum of two HAM/TSP patients with HBZ-specific antibody responses.

Mentions: Since strong antibody responses against HTLV-1 antigens have been reported in both serum and CSF of HAM/TSP patients [10,32], we also 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. Antibody responses for Gag, Env and Tax were detected in both serum and CSF samples of all five HAM/TSP patients (Figure 3A-C). Antibody responses for HBZ were only detected in CSF samples of HAM/TSP patients (#1 and #2) with HBZ-specific antibody responses in serum, but not in HAM/TSP patients (#5, #6 and #7) who were negative for HBZ-specific immunoreactivity in serum (Figure 3D). Moreover, HBZ-specific antibody responses in CSF were detected at lower levels compared to serum (Figure 3D). Comparison of antibody responses between CSF and serum revealed that the ratio of anti-HBZ antibody in CSF to serum was lower than the ratio of anti-Gag, anti-Env and anti-Tax in CSF to serum (Figure 3E).


Humoral immune response to HTLV-1 basic leucine zipper factor (HBZ) in HTLV-1-infected individuals.

Enose-Akahata Y, Abrams A, Massoud R, Bialuk I, Johnson KR, Green PL, Maloney EM, Jacobson S - Retrovirology (2013)

Detection of antibody responses against HTLV-1 in serum and CSF of HAM/TSP patients. The data were obtained from 5 HAM/TSP patients including 2 patients (#1 and #2) and 3 patients (#5, #6 and #7) with and without HBZ-specific antibody response, respectively. Antibody responses for Gag (A), Env (B), Tax (C) and HBZ (D) were examined in serum (opened bar) and in CSF (closed bar). (E) Ratio of immunoreactivities against HTLV-1 Gag, Env, Tax and HBZ in CSF to those in serum of two HAM/TSP patients with HBZ-specific antibody responses.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3584941&req=5

Figure 3: Detection of antibody responses against HTLV-1 in serum and CSF of HAM/TSP patients. The data were obtained from 5 HAM/TSP patients including 2 patients (#1 and #2) and 3 patients (#5, #6 and #7) with and without HBZ-specific antibody response, respectively. Antibody responses for Gag (A), Env (B), Tax (C) and HBZ (D) were examined in serum (opened bar) and in CSF (closed bar). (E) Ratio of immunoreactivities against HTLV-1 Gag, Env, Tax and HBZ in CSF to those in serum of two HAM/TSP patients with HBZ-specific antibody responses.
Mentions: Since strong antibody responses against HTLV-1 antigens have been reported in both serum and CSF of HAM/TSP patients [10,32], we also 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. Antibody responses for Gag, Env and Tax were detected in both serum and CSF samples of all five HAM/TSP patients (Figure 3A-C). Antibody responses for HBZ were only detected in CSF samples of HAM/TSP patients (#1 and #2) with HBZ-specific antibody responses in serum, but not in HAM/TSP patients (#5, #6 and #7) who were negative for HBZ-specific immunoreactivity in serum (Figure 3D). Moreover, HBZ-specific antibody responses in CSF were detected at lower levels compared to serum (Figure 3D). Comparison of antibody responses between CSF and serum revealed that the ratio of anti-HBZ antibody in CSF to serum was lower than the ratio of anti-Gag, anti-Env and anti-Tax in CSF to serum (Figure 3E).

Bottom Line: Immunoreactivity against HBZ was detected in subsets of all HTLV-1-infected individuals but the test did not discriminate between AC, ATL and HAM/TSP.This 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.

ABSTRACT

Background: 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. 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.

Results: Immunoreactivity 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.

Conclusions: This 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.

Show MeSH
Related in: MedlinePlus