Conservation of a Neutralization Epitope of Human T-cell Leukemia Virus Type 1 (HTLV-1) among Currently Endemic Clinical Isolates in Okinawa, Japan
Conservation of a Neutralization Epitope of Human T-cell Leukemia Virus Type 1 (HTLV-1) among Currently Endemic Clinical Isolates in Okinawa, Japan
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DOI：
10.3390/pathogens9020082
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发表时间：
2020-02-01
期刊：
影响因子：
3.7
通讯作者：
Tanaka, Yuetsu
中科院分区：
文献类型：
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作者：
Mizuguchi, Mariko;Takahashi, Yoshiaki;Tanaka, Yuetsu
在全球1000万人类T细胞白血病病毒1型(HTLV-1)携带者中，约有十分之一生活在日本。这些感染者大多生活在日本西南部地区，包括冲绳县；但目前还没有针对HTLV-1感染的预防性疫苗。为了防止HTLV-1的传播，我们先前制备了一种人源化的单抗(Hu-LAT-27)，它既能介导中和作用，又能介导抗体依赖的细胞杀伤作用(ADCC)。LAT-27的中和表位是HTLV-1膜蛋白gp46蛋白191~196位的线性氨基酸序列(Leu-Pro-His-Ser-Asn-Leu)。在这里，我们发现在冲绳流行的HTLV-1临床分离株中LAT-27表位被很好地保守。HU-LAT-27处理抑制了这些HTLV-1临床分离株的合胞体形成。虽然在少数HTLV-1分离株中发现LAT-27表位的192位氨基酸发生了从脯氨酸到丝氨酸的替换，但Hu-LAT-27仍能与带有该氨基酸替换的合成肽发生反应。这些发现证明了Hu-LAT-27的广谱反应性，提示Hu-LAT-27可能是预防HTLV-1感染的被动免疫的候选药物。
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.