Absolute quantification of HTLV-1 basic leucine zipper factor (HBZ) protein and its plasma antibody in HTLV-1 infected individuals with different clinical status

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Abstract

Background

Human T cell leukemia virus type 1 (HTLV-1) basic leucine zipper factor (HBZ), which is encoded by a minus strand mRNA, is thought to play important roles in the development of adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). However, a comprehensive analysis of HBZ, including mRNA and protein expression, humoral immunoreactivity against HBZ, and HTLV-1 proviral load (PVL), in HTLV-1-infected individuals with different clinical status has not been reported previously.

Results

In this study, using novel monoclonal antibody-based in-house enzyme-linked immunosorbent assay systems, we report the absolute quantification of HBZ protein and its plasma antibody in clinical samples from HTLV-1-infected individuals with different clinical status. The data were compared to both HBZ mRNA levels and PVL. The results showed that plasma anti-HBZ antibody was detectable only in 10.4 % (5/48) of asymptomatic carriers (ACs), 10.8 % (13/120) of HAM/TSP patients, and 16.7 % (7/42) of ATL patients. HBZ protein was detected in three out of five patients with acute ATL, but was not detected in patients with HAM/TSP (0/10) or ACs (0/4). Thus, an antibody response to HBZ was not associated with the PVL or the expression of HBZ (both at the mRNA and protein levels) or the clinical status of the infection.

Conclusions

The present results emphasize the extremely low expression and immunogenicity of HBZ in natural HTLV-1 infection. However, there is a possibility that the low but distinct expression of HBZ protein in PBMCs is associated with the survival of HTLV-1-infected cells and the development of ATL.

Electronic supplementary material

The online version of this article (doi:10.1186/s12977-016-0263-z) contains supplementary material, which is available to authorized users.

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Most cited references 21

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Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma. A report from the Lymphoma Study Group (1984-87).

M. Shimoyama (1991)

The following diagnostic criteria are proposed to classify four clinical subtypes of HTLV-1 associated adult T-cell leukaemia-lymphoma (ATL): (1) Smouldering type, 5% or more abnormal lymphocytes of T-cell nature in PB, normal lymphocyte level (less than 4 x 10(9)/l), no hypercalcaemia (corrected calcium level less than 2.74 mmol/l), lactate dehydrogenase (LDH) value of up to 1.5 x the normal upper limit, no lymphadenopathy, no involvement of liver, spleen, central nervous system (CNS), bone and gastrointestinal tract, and neither ascites nor pleural effusion. Skin and pulmonary lesion(s) may be present. In case of less than 5% abnormal T-lymphocytes in PB, at least one of histologically-proven skin and pulmonary lesions should be present. (2) Chronic type, absolute lymphocytosis (4 x 10(9)/l or more) with T-lymphocytosis more than 3.5 x 10(9)/l, LDH value up to twice the normal upper limit, no hypercalcaemia, no involvement of CNS, bone and gastrointestinal tract, and neither ascites nor pleural effusion. Lymphadenopathy and involvement of liver, spleen, skin, and lung may be present, and 5% or more abnormal T-lymphocytes are seen in PB in most cases . (3) Lymphoma type, no lymphocytosis, 1% or less abnormal T-lymphocytes, and histologically-proven lymphadenopathy with or without extranodal lesions. (4) Acute type, remaining ATL patients who have usually leukaemic manifestation and tumour lesions, but are not classified as any of the three other types. A total of 818 ATL patients with a mean age of 57 years, newly diagnosed from 1983 to 1987, were analysed by this criteria. There were 448 males and 370 females, and 253 were still alive with a median follow-up time of 13.3 months from diagnosis, while 565 were dead with a median survival time (MST) of 5.4 months. MST was 6.2 months for acute type, 10.2 months for lymphoma type, 24.3 months for chronic type, and not yet reached for smouldering type. Projected 2- and 4-year survival rates were 16.7% and 5.0% for acute type, 21.3% and 5.7% for lymphoma type, 52.4% and 26.9% for chronic type, 77.7% and 62.8% for smouldering type, respectively. Distinct clinical features and laboratory findings of each clinical subtype are described.

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Adult T-cell leukemia: antigen in an ATL cell line and detection of antibodies to the antigen in human sera.

Y Hinuma, K. Nagata, M Hanaoka … (1981)

Indirect immunofluorescence of certain human sera demonstrated an antigen(s) in the cytoplasm of 1--5% of the cells of a T-cell line, MT-1, from a patient with adult T-cell leukemia (ATL), which is endemic in southwestern Japan. The antigen was not detected in other human lymphoid cell lines, including six T-cell lines, seven B-cell lines, and four non-T non-B cell lines. The antigen did not show cross antigenicity with that of herpesviruses, including Epstein--Barr virus, herpes simplex virus, cytomegalovirus, varicella-zoster virus, herpesvirus saimiri, and Marek disease virus. The proportion of antigen-bearing cells was increased by a factor of approximately 5 on culture in the presence of 5-iodo-2'-deoxyuridine. Antibodies against the antigen in MT-1 cells were found in all 44 patients with ATL examined and in 32 of 40 patients with malignant T-cell lymphomas (most of them had diseases similar to ATL except that leukemic cells were not found in the peripheral blood). The antibodies were also detected in 26% of the healthy adults examined from ATL-endemic areas but in only a few of those examined from ATL-non-endemic areas. On electron microscopy, extracellular type C virus particles were detected in pelleted MT-1 cells cultured in the presence of 5-iodo-2'-deoxyuridine.

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HTLV-I associated myelopathy, a new clinical entity.

S Izumo, A Igata, Alvin Matsumoto … (1986)

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Author and article information

Contributors

Yasuo Shiohama: shiohama@bioreg.kyushu-u.ac.jp

Tadasuke Naito: tadanaito@med.kawasaki-m.ac.jp

Toshio Matsuzaki: zaki7@mta.biglobe.ne.jp

Reiko Tanaka: reiko_tanaka@s5.dion.ne.jp

Takeaki Tomoyose: ttomoyos@ryudai2nai.com

Hiroshi Takashima: thiroshi@m3.kufm.kagoshima-u.ac.jp

Takuya Fukushima: fukutaku@med.u-ryukyu.ac.jp

Yuetsu Tanaka: yuetsu@s4.dion.ne.jp

Mineki Saito: +81-86-462-1111 , mineki@med.kawasaki-m.ac.jp

Journal

Journal ID (nlm-ta): Retrovirology

Journal ID (iso-abbrev): Retrovirology

Title: Retrovirology

Publisher: BioMed Central (London )

ISSN (Electronic): 1742-4690

Publication date (Electronic): 27 April 2016

Publication date PMC-release: 27 April 2016

Publication date Collection: 2016

Volume: 13

Electronic Location Identifier: 29

Affiliations

[ ]Department of Microbiology, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192 Japan

[ ]Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520 Japan

[ ]Department of Immunology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215 Japan

[ ]Division of Endocrinology, Diabetes and Metabolism, Hematology and Rheumatology, Second Department of Internal Medicine, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215 Japan

[ ]Laboratory of Hematoimmnology, School of Health Sciences, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215 Japan

[ ]Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, 812-8582 Japan

Article

Publisher ID: 263

DOI: 10.1186/s12977-016-0263-z

PMC ID: 4847349

PubMed ID: 27117327

SO-VID: 0bf7b535-3a3b-48dd-b097-e9ceb061d6f4

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 27 January 2016

Date accepted : 18 April 2016

Funding

Funded by: KAKENHI

Award ID: 21590512

Award ID: 24590556

Award ID: 15K09345

Award Recipient : Mineki Saito

Funded by: Health and Labor Sciences Research Grants

Award ID: H22-013

Award ID: H23-126

Award ID: H25-023

Award ID: H25-028

Award Recipient : Mineki Saito

Funded by: The Japan Agency for Medical Research and Development (AMED)

Funded by: The Project of Establishing Medical Research Base Networks against Infectious Diseases in Okinawa

Funded by: The Novartis Foundation for the Promotion of Science

Funded by: The Joint Usage/Research Center Program of the Institute for Virus Research, Kyoto University

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ScienceOpen disciplines: Microbiology & Virology

Keywords: htlv-1,hbz,atl,monoclonal antibody,elisa

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ScienceOpen disciplines: Microbiology & Virology

Keywords: htlv-1, hbz, atl, monoclonal antibody, elisa

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Absolute quantification of HTLV-1 basic leucine zipper factor (HBZ) protein and its plasma antibody in HTLV-1 infected individuals with different clinical status

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Abstract

Background

Results

Conclusions

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Role of Microbes in Soil Fertility and Human Health

Most cited references 21

Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma. A report from the Lymphoma Study Group (1984-87).

Adult T-cell leukemia: antigen in an ATL cell line and detection of antibodies to the antigen in human sera.

HTLV-I associated myelopathy, a new clinical entity.

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