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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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Related in: MedlinePlus

Comparison of antibody responses against HTLV-1, proviral loads and HBZ mRNA expression of HTLV-1-infected individuals. Comparison of antibody responses against Gag (A), Env (B) and Tax (C) in serum/plasma of HTLV-1-infected individuals with and without antibody response against HBZ by Mann–Whitney Test. The data were obtained from 338 HTLV-1-infected individuals; 145 AC, 89 ATL patients and 104 HAM/TSP patients. Anti-HBZ (−) group includes 130 AC, 78 ATL patients and 90 HAM/TSP patients. Anti-HBZ (+) group includes 15 AC, 11 ATL patients and 14 HAM/TSP patients. The horizontal line represents the mean. (D) Correlation of HTLV-1 proviral load with HBZ mRNA expression in 13 HAM/TSP patients including 6 patients with antibody response against HBZ (closed circles) and 7 patients without antibody response against HBZ (closed triangles) by Spearman’s correlation test. (E) Comparison of HTLV-1 proviral loads between HAM/TSP patients with and without antibody response against HBZ. HTLV-1 proviral loads were examined in PBMCs of HAM/TSP patients using Mann–Whitney Test. The horizontal line represents the mean. (F) Comparison of HBZ mRNA expression between HAM/TSP patients with and without antibody response against HBZ. The expression of HBZ mRNA was examined in PBMCs of HAM/TSP patients using Mann–Whitney Test. The horizontal line represents the mean. (G) Correlation of immunoreactivity against HBZ with HTLV-1 proviral loads (closed circles) and HBZ mRNA expression (opened circles) in 6 HAM/TSP patients with antibody response against HBZ by Spearman’s correlation test.
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Figure 2: Comparison of antibody responses against HTLV-1, proviral loads and HBZ mRNA expression of HTLV-1-infected individuals. Comparison of antibody responses against Gag (A), Env (B) and Tax (C) in serum/plasma of HTLV-1-infected individuals with and without antibody response against HBZ by Mann–Whitney Test. The data were obtained from 338 HTLV-1-infected individuals; 145 AC, 89 ATL patients and 104 HAM/TSP patients. Anti-HBZ (−) group includes 130 AC, 78 ATL patients and 90 HAM/TSP patients. Anti-HBZ (+) group includes 15 AC, 11 ATL patients and 14 HAM/TSP patients. The horizontal line represents the mean. (D) Correlation of HTLV-1 proviral load with HBZ mRNA expression in 13 HAM/TSP patients including 6 patients with antibody response against HBZ (closed circles) and 7 patients without antibody response against HBZ (closed triangles) by Spearman’s correlation test. (E) Comparison of HTLV-1 proviral loads between HAM/TSP patients with and without antibody response against HBZ. HTLV-1 proviral loads were examined in PBMCs of HAM/TSP patients using Mann–Whitney Test. The horizontal line represents the mean. (F) Comparison of HBZ mRNA expression between HAM/TSP patients with and without antibody response against HBZ. The expression of HBZ mRNA was examined in PBMCs of HAM/TSP patients using Mann–Whitney Test. The horizontal line represents the mean. (G) Correlation of immunoreactivity against HBZ with HTLV-1 proviral loads (closed circles) and HBZ mRNA expression (opened circles) in 6 HAM/TSP patients with antibody response against HBZ by Spearman’s correlation test.

Mentions: Since HBZ-specific immunoreactivity was detected in a subset of HTLV-1 infected subjects, we asked whether there is any relationship between HBZ-specific immunoreactivity and other immunological and virological markers of HTLV-1 infection, such as antibody responses to other HTLV-1 proteins and HTLV-1 viral gene expression. Antibody responses against Gag, Env or Tax did not differ significantly between HTLV-1-infected individuals with or without HBZ-specific immunoreactivity (Figure 2A-C). We also compared HTLV-1 proviral load and HBZ mRNA expression between HTLV-1-infected individuals with and without HBZ-specific immunoreactivity. Since PBMC were unavailable for the Jamaican subjects, cells were obtained from NIH HAM/TSP patients whose serum was tested for anti-HBZ antibody responses. These 13 HAM/TSP patients showed a range of HTLV-1 proviral loads in PBMCs between 5.6 and 87.8% (Figure 2D). Consistent with a previous report [27], HBZ mRNA was detectable in PBMCs of HAM/TSP patients and significantly correlated with proviral loads (Figure 2D). There was no significant difference of proviral loads between individuals with and without HBZ-specific immunoreactivity (Figure 2E); there was also no significant correlation between proviral load and the HBZ-specific antibody responses (Figure 2G). Moreover, the mean expression of HBZ mRNA from HAM/TSP patients’ PBMC was not associated with the detection of HBZ immunoreactivity (Figure 2F) or magnitude of serum anti-HBZ antibodies (Figure 2G). Thus, antibody responses for HBZ did not correlate with proviral loads or HBZ mRNA expression in HAM/TSP patients, consistent with previous studies that also failed to demonstrate a correlation between HBZ mRNA expression and HTLV-1 antibody titer in serum [27].


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)

Comparison of antibody responses against HTLV-1, proviral loads and HBZ mRNA expression of HTLV-1-infected individuals. Comparison of antibody responses against Gag (A), Env (B) and Tax (C) in serum/plasma of HTLV-1-infected individuals with and without antibody response against HBZ by Mann–Whitney Test. The data were obtained from 338 HTLV-1-infected individuals; 145 AC, 89 ATL patients and 104 HAM/TSP patients. Anti-HBZ (−) group includes 130 AC, 78 ATL patients and 90 HAM/TSP patients. Anti-HBZ (+) group includes 15 AC, 11 ATL patients and 14 HAM/TSP patients. The horizontal line represents the mean. (D) Correlation of HTLV-1 proviral load with HBZ mRNA expression in 13 HAM/TSP patients including 6 patients with antibody response against HBZ (closed circles) and 7 patients without antibody response against HBZ (closed triangles) by Spearman’s correlation test. (E) Comparison of HTLV-1 proviral loads between HAM/TSP patients with and without antibody response against HBZ. HTLV-1 proviral loads were examined in PBMCs of HAM/TSP patients using Mann–Whitney Test. The horizontal line represents the mean. (F) Comparison of HBZ mRNA expression between HAM/TSP patients with and without antibody response against HBZ. The expression of HBZ mRNA was examined in PBMCs of HAM/TSP patients using Mann–Whitney Test. The horizontal line represents the mean. (G) Correlation of immunoreactivity against HBZ with HTLV-1 proviral loads (closed circles) and HBZ mRNA expression (opened circles) in 6 HAM/TSP patients with antibody response against HBZ by Spearman’s correlation test.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Comparison of antibody responses against HTLV-1, proviral loads and HBZ mRNA expression of HTLV-1-infected individuals. Comparison of antibody responses against Gag (A), Env (B) and Tax (C) in serum/plasma of HTLV-1-infected individuals with and without antibody response against HBZ by Mann–Whitney Test. The data were obtained from 338 HTLV-1-infected individuals; 145 AC, 89 ATL patients and 104 HAM/TSP patients. Anti-HBZ (−) group includes 130 AC, 78 ATL patients and 90 HAM/TSP patients. Anti-HBZ (+) group includes 15 AC, 11 ATL patients and 14 HAM/TSP patients. The horizontal line represents the mean. (D) Correlation of HTLV-1 proviral load with HBZ mRNA expression in 13 HAM/TSP patients including 6 patients with antibody response against HBZ (closed circles) and 7 patients without antibody response against HBZ (closed triangles) by Spearman’s correlation test. (E) Comparison of HTLV-1 proviral loads between HAM/TSP patients with and without antibody response against HBZ. HTLV-1 proviral loads were examined in PBMCs of HAM/TSP patients using Mann–Whitney Test. The horizontal line represents the mean. (F) Comparison of HBZ mRNA expression between HAM/TSP patients with and without antibody response against HBZ. The expression of HBZ mRNA was examined in PBMCs of HAM/TSP patients using Mann–Whitney Test. The horizontal line represents the mean. (G) Correlation of immunoreactivity against HBZ with HTLV-1 proviral loads (closed circles) and HBZ mRNA expression (opened circles) in 6 HAM/TSP patients with antibody response against HBZ by Spearman’s correlation test.
Mentions: Since HBZ-specific immunoreactivity was detected in a subset of HTLV-1 infected subjects, we asked whether there is any relationship between HBZ-specific immunoreactivity and other immunological and virological markers of HTLV-1 infection, such as antibody responses to other HTLV-1 proteins and HTLV-1 viral gene expression. Antibody responses against Gag, Env or Tax did not differ significantly between HTLV-1-infected individuals with or without HBZ-specific immunoreactivity (Figure 2A-C). We also compared HTLV-1 proviral load and HBZ mRNA expression between HTLV-1-infected individuals with and without HBZ-specific immunoreactivity. Since PBMC were unavailable for the Jamaican subjects, cells were obtained from NIH HAM/TSP patients whose serum was tested for anti-HBZ antibody responses. These 13 HAM/TSP patients showed a range of HTLV-1 proviral loads in PBMCs between 5.6 and 87.8% (Figure 2D). Consistent with a previous report [27], HBZ mRNA was detectable in PBMCs of HAM/TSP patients and significantly correlated with proviral loads (Figure 2D). There was no significant difference of proviral loads between individuals with and without HBZ-specific immunoreactivity (Figure 2E); there was also no significant correlation between proviral load and the HBZ-specific antibody responses (Figure 2G). Moreover, the mean expression of HBZ mRNA from HAM/TSP patients’ PBMC was not associated with the detection of HBZ immunoreactivity (Figure 2F) or magnitude of serum anti-HBZ antibodies (Figure 2G). Thus, antibody responses for HBZ did not correlate with proviral loads or HBZ mRNA expression in HAM/TSP patients, consistent with previous studies that also failed to demonstrate a correlation between HBZ mRNA expression and HTLV-1 antibody titer in serum [27].

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