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对不同临床状态的人类嗜T淋巴细胞病毒1型(HTLV-1)感染者体内HTLV-1碱性亮氨酸拉链因子(HBZ)蛋白及其血浆抗体进行绝对定量分析。

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

作者信息

Shiohama Yasuo, Naito Tadasuke, Matsuzaki Toshio, Tanaka Reiko, Tomoyose Takeaki, Takashima Hiroshi, Fukushima Takuya, Tanaka Yuetsu, Saito Mineki

机构信息

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

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

出版信息

Retrovirology. 2016 Apr 27;13:29. doi: 10.1186/s12977-016-0263-z.

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.

摘要

背景

人类T细胞白血病病毒1型(HTLV-1)碱性亮氨酸拉链因子(HBZ)由负链mRNA编码,被认为在成人T细胞白血病(ATL)和HTLV-1相关脊髓病/热带痉挛性截瘫(HAM/TSP)的发展中起重要作用。然而,此前尚未有针对不同临床状态的HTLV-1感染个体进行的HBZ综合分析报告,包括mRNA和蛋白质表达、针对HBZ的体液免疫反应以及HTLV-1前病毒载量(PVL)。

结果

在本研究中,我们使用基于新型单克隆抗体的内部酶联免疫吸附测定系统,报告了来自不同临床状态的HTLV-1感染个体临床样本中HBZ蛋白及其血浆抗体的绝对定量。将数据与HBZ mRNA水平和PVL进行了比较。结果显示,仅在10.4%(5/48)的无症状携带者(ACs)、10.8%(13/120)的HAM/TSP患者和16.7%(7/42)的ATL患者中可检测到血浆抗HBZ抗体。在5例急性ATL患者中有3例检测到HBZ蛋白,但在HAM/TSP患者(0/10)或ACs患者(0/4)中未检测到。因此,针对HBZ的抗体反应与PVL、HBZ的表达(mRNA和蛋白质水平)或感染的临床状态无关。

结论

目前的结果强调了HBZ在自然HTLV-1感染中的极低表达和免疫原性。然而,外周血单个核细胞中HBZ蛋白低但明显的表达有可能与HTLV-1感染细胞的存活及ATL的发展相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1588/4847349/d334f1525cd2/12977_2016_263_Fig1_HTML.jpg

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