在伊朗东北部马什哈德的 ATLL 患者中，完整的人类 T 细胞白血病病毒 1 序列揭示了一个过早终止的蛋白酶和一个伸长的 pX 开放阅读框 III。

Complete sequence of human T cell leukemia virus type 1 in ATLL patients from Northeast Iran, Mashhad revealed a prematurely terminated protease and an elongated pX open reading frame III.

机构信息

Immunology Research Center, Division of Inflammation and Inflammatory Diseases, Mashhad University of Medical Sciences, Mashhad, Iran.

Department of Internal Medicine, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Infect Genet Evol. 2019 Sep;73:460-469. doi: 10.1016/j.meegid.2019.05.012. Epub 2019 May 16.

DOI:10.1016/j.meegid.2019.05.012

PMID:31102740

Abstract

To gain insight into the origin, evolution, dissemination and viral factors affecting HTLV-1-associated diseases, knowing the complete viral genome sequences is important. So far, no full-length HTLV-1 genome sequence has been reported from Iran. Here we report the complete nucleotide sequence of HTLV-1 viruses isolated from adult T cell leukemia/lymphoma (ATLL) patients from this region. The genome size of HTLV-1-MhD (Mashhad) was found to be 9036 bp and sequence analysis of the LTR region showed that it belongs to cosmopolitan subtype A. Comparing the sequences with isolates from another endemic area (HTLV-1ATK) revealed variations in the U3 region (~3.4%), while there was 99.1% and 97.0% similarity in R and U5 regions, respectively. The nucleotide sequences of HTLV-1 gag, pro and pol genes had a difference of 1.1% compared with HTLV-1 ATK with 16 nucleotides replaced in the gag and 27 in the pol regions. There was no variability in the amino acid sequences in the p24, however three residues were different in the p19 and one in the p15. The nucleotide sequence of env showed a divergence of 1.5% compared to ATK with 22-nucleotide variation. The HTLV-1-MhD Tax, p13, p30, and p12 had 99.1, 100, 98.8, and 98%, respectively similarity with the prototype strain. Four amino acid changes were detected in ORF1 and ORF2 products p12 and p30, respectively, while the p13 region showed 100% conservation. The nucleotide identity between the isolates of Mashhad and those isolated from France, Germany, China, Canada and Brazil was 99.1%, 99.2%, 97.9%, 99% and 99.3%, respectively. Four amino acid changes compared with HTLV-1ATK from Japan were detected in ORF1 and ORF2 products p12 and p30, respectively, while the p13 region showed 100% conservation. This data could provide information regarding the evolutionary history, phylogeny, origin of the virus and vaccine design.

摘要

为了深入了解 HTLV-1 相关疾病的起源、进化、传播和病毒因素，了解完整的病毒基因组序列是很重要的。到目前为止，还没有报道来自伊朗的全长 HTLV-1 基因组序列。在这里，我们报告了从该地区成人 T 细胞白血病/淋巴瘤（ATLL）患者中分离的 HTLV-1 病毒的完整核苷酸序列。HTLV-1-MhD（马什哈德）的基因组大小为 9036bp，对 LTR 区域的序列分析表明它属于世界性亚型 A。将这些序列与另一个流行地区（HTLV-1ATK）的分离株进行比较，发现 U3 区域的序列存在差异（~3.4%），而 R 和 U5 区域的序列分别有 99.1%和 97.0%的相似性。与 HTLV-1ATK 相比，HTLV-1 gag、pro 和 pol 基因的核苷酸序列有 1.1%的差异，gag 区有 16 个核苷酸被取代，pol 区有 27 个核苷酸被取代。p24 区的氨基酸序列没有变化，但是 p19 区有三个残基不同，p15 区有一个残基不同。与 ATK 相比，env 区的核苷酸序列有 1.5%的差异，有 22 个核苷酸发生了变异。HTLV-1-MhD 的 Tax、p13、p30 和 p12 与原型株的相似度分别为 99.1%、100%、98.8%和 98%。ORF1 和 ORF2 产物 p12 和 p30 中的 ORF1 和 ORF2 产物分别检测到 4 个氨基酸变化，而 p13 区则完全保守。马什哈德分离株与来自法国、德国、中国、加拿大和巴西的分离株的核苷酸同一性分别为 99.1%、99.2%、97.9%、99%和 99.3%。与来自日本的 HTLV-1ATK 相比，ORF1 和 ORF2 产物 p12 和 p30 中分别检测到 4 个氨基酸变化，而 p13 区则完全保守。这些数据可以为病毒的进化历史、系统发生、起源和疫苗设计提供信息。