Characterization and sequencing of prototypic human T-lymphotropic virus type 1 (HTLV-1) from an HTLV-1/2 seroindeterminate patient.

Characterization and sequencing of prototypic human T-lymphotropic virus type 1 (HTLV-1) from an HTLV-1/2 seroindeterminate patient.
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来自 HTLV-1/2 血清不确定患者的原型人类 T 淋巴细胞病毒 1 型 (HTLV-1) 的表征和测序。

DOI:
10.1128/jvi.74.5.2178-2185.2000
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发表时间:
2000
影响因子:
5.4
通讯作者:
Jacobson,S
Jacobson,S
中科院分区:
医学2区
文献类型:
--
作者:
Waziri,A;Soldan,SS;Graf,MD;Nagle,J;Jacobson,S

文献摘要

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人类嗜T淋巴细胞病毒1型(HTLV-1)的血清学筛查与人类免疫缺陷病毒(HIV)的标准筛查过程平行,其中通过酶联免疫吸附试验(ELISA)发现阳性的样本采用改良的蛋白质印迹法进行确认。在大量病例中,HTLV-1/2 ELISA阳性标本在Western印迹上显示不完整的带型。提供这些非典型抗体应答的个体被归类为HTLV-1/2血清不确定。虽然HTLV-1基因组序列在血清阳性个体的外周血淋巴细胞(PBL)中容易检测到,但以前的研究反复证明,来自绝大多数HTLV-1/2血清不确定个体的PBL对HTLV-1是PCR阴性的。因此,鉴定负责这种不确定反应性的试剂一直很有意义。我们已经从这些血清不确定的个体中产生了HTLV-1阳性B细胞系(SI-1 B)。既往对该患者外周血淋巴细胞进行的HTLV-1筛查,经一级PCR检测均为阴性;然而,巢式PCR定期检测到HTLV-1 tax。用来自SI-1 B细胞系的基因组DNA和HTLV-1特异性引物产生的DNA序列数据证明存在与HTLV-1的Cosmopolitan形式具有> 97%同源性的全长病毒基因组。在3 ′-gag/5 ′-protregion中发现了一个12 bp的缺失,这将预测这些基因的改变或无功能蛋白的翻译。我们提出,这HTLV-1/2血清确定的患者感染了HTLV-1的原型形式在一个极低的病毒载量,这一发现可以解释HTLV-1/2血清确定的反应,至少在这些人的一个子集。
Serological screening for human T-lymphotropic virus type 1 (HTLV-1) parallels the standard screening process for human immunodeficiency virus (HIV), in which samples found positive by enzyme-linked immunosorbent assay (ELISA) are confirmed with a modified Western blot procedure. There are a significant number of cases in which HTLV-1/2 ELISA-positive specimens demonstrate an incomplete banding pattern on this Western blot. Individuals providing these atypical antibody responses are categorized as seroindeterminate for HTLV-1/2. Although HTLV-1 genomic sequences are readily detectable in the peripheral blood lymphocytes (PBL) of seropositive individuals, previous studies have repeatedly demonstrated that PBL from the vast majority of HTLV-1/2 seroindeterminate individuals are PCR negative for HTLV-1. As a result, identification of the agent responsible for this indeterminate reactivity has been of interest. We have generated an HTLV-1-positive B-cell line (SI-1 B) from one of these seroindeterminate individuals. Previous screening for HTLV-1 in PBL from this patient had been routinely negative by primary PCR; however, HTLV-1taxhad been periodically detected by nested PCR. DNA sequence data generated with genomic DNA from the SI-1 B cell line and HTLV-1-specific primers demonstrated the presence of a full-length viral genome with >97% homology to the Cosmopolitan form of HTLV-1. A 12-bp deletion was identified in the 3′-gag/5′-protregion, which would predict translation of altered or nonfunctional proteins from these genes. We propose that this HTLV-1/2-seroindeterminate patient is infected with a prototypic form of HTLV-1 at an extremely low viral load and that this finding may explain HTLV-1/2 seroindeterminate reactivity in at least a subset of these individuals.