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日本冲绳目前流行的人类T细胞白血病病毒1型(HTLV-1)临床分离株中中和表位的保守性

Conservation of a Neutralization Epitope of Human T-cell Leukemia Virus Type 1 (HTLV-1) among Currently Endemic Clinical Isolates in Okinawa, Japan.

作者信息

Mizuguchi Mariko, Takahashi Yoshiaki, Tanaka Reiko, Fukushima Takuya, Tanaka Yuetsu

机构信息

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

Laboratory of Hematoimmunology, School of Health Sciences, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Okinawa 903-0215, Japan.

出版信息

Pathogens. 2020 Jan 27;9(2):82. doi: 10.3390/pathogens9020082.

Abstract

Approximately one-tenth of the 10 million individuals living with human T-cell leukemia virus type-1 (HTLV-1) worldwide live in Japan. Most of these infected individuals live in the southwest region of Japan, including Okinawa prefecture; however, currently no prophylactic vaccine against HTLV-1 infection is available. For preventing the HTLV-1 spread, we previously generated a humanized monoclonal antibody (hu-LAT-27) that mediates both neutralization and antibody-dependent cellular cytotoxicity (ADCC). The neutralization epitope of LAT-27 is a linear amino acid sequence from residue 191 to 196 (Leu-Pro-His-Ser-Asn-Leu) of the HTLV-1 envelope gp46 protein. Here, we found that the LAT-27 epitope is well conserved among HTLV-1 clinical isolates prevalent in Okinawa. The hu-LAT-27 treatment inhibited syncytium formation by these clinical HTLV-1 isolates. Although an amino acid substitution at residue 192 in the LAT-27 epitope from proline to serine was found in a few HTLV-1 isolates, hu-LAT-27 could still react with a synthetic peptide carrying this amino acid substitution. These findings demonstrate the wide spectrum of hu-LAT-27 reactivity, suggesting that hu-LAT-27 may be a candidate drug for prophylactic passive immunization against HTLV-1 infection.

摘要

全球约1000万感染人类T细胞白血病病毒1型(HTLV-1)的人中,约十分之一生活在日本。这些受感染个体大多生活在日本西南部地区,包括冲绳县;然而,目前尚无针对HTLV-1感染的预防性疫苗。为防止HTLV-1传播,我们之前制备了一种人源化单克隆抗体(hu-LAT-27),它能介导中和作用和抗体依赖性细胞毒性(ADCC)。LAT-27的中和表位是HTLV-1包膜糖蛋白gp46第191至196位残基(亮氨酸-脯氨酸-组氨酸-丝氨酸-天冬酰胺-亮氨酸)的线性氨基酸序列。在此,我们发现LAT-27表位在冲绳流行的HTLV-1临床分离株中高度保守。hu-LAT-27处理可抑制这些临床HTLV-1分离株诱导的合胞体形成。虽然在少数HTLV-1分离株中发现LAT-27表位第192位残基的脯氨酸被丝氨酸取代,但hu-LAT-27仍能与携带此氨基酸取代的合成肽发生反应。这些发现证明了hu-LAT-27反应性的广谱性,提示hu-LAT-27可能是预防HTLV-1感染的被动免疫候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f93e/7168584/b633f3a4d613/pathogens-09-00082-g001.jpg

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