Murakami Yuji, Hasegawa Atsuhiko, Ando Satomi, Tanaka Reiko, Masuda Takao, Tanaka Yuetsu, Kannagi Mari
Department of Immunotherapeutics, Tokyo Medical and Dental University, Tokyo, Japan.
Department of Immunology, University of the Ryukyus, Okinawa, Japan.
J Gen Virol. 2017 Apr;98(4):835-846. doi: 10.1099/jgv.0.000733. Epub 2017 May 5.
Human T-cell leukaemia virus type 1 (HTLV-1) is a human retrovirus that is a causative agent of adult T-cell leukaemia/lymphoma (ATL) and is mainly transmitted from an infected mother to her child via breastfeeding. Such an HTLV-1 infection during childhood is believed to be a risk factor for ATL development. Although it has been suggested that an increased proviral load (PVL), a higher titre of antibody (Ab) in the infected mother and prolonged breastfeeding are associated with an increased risk of mother-to-child transmission (MTCT), the mechanisms underlying MTCT of HTLV-1 remain largely unknown. In this study, we developed an MTCT model using orally HTLV-1-infected rats that have no Ab responses against viral antigens, such as Gag and Env. In this model, HTLV-1 could be transmitted from the infected mother rats to their offspring at a high rate (50-100 %), and the rate of MTCT tended to be correlated with the PVL of the infected mother rats. Furthermore, passive immunization of uninfected adult rats and an infected mother rat with a rat anti-HTLV-1 Env gp46-neutralizing mAb was unable to suppress primary oral HTLV-1 infection to the adult rats and vertical HTLV-1 transmission to the offspring, respectively. Our findings indicate that this MTCT model would be useful to investigate not only the mechanisms of MTCT but also the role of anti-HTLV-1 Ab in MTCT of HTLV-1. They also provide some information on the role of maternal Abs in MTCT, which should be considered when designing a strategy for prevention of MTCT of HTLV-1.
人类T细胞白血病病毒1型（HTLV-1）是一种人类逆转录病毒，是成人T细胞白血病/淋巴瘤（ATL）的病原体，主要通过母乳喂养从感染母亲传播给孩子。儿童期感染这种HTLV-1被认为是ATL发生的危险因素。尽管有人提出，前病毒载量（PVL）增加、感染母亲体内抗体（Ab）滴度较高以及母乳喂养时间延长与母婴传播（MTCT）风险增加有关，但HTLV-1母婴传播的潜在机制在很大程度上仍不清楚。在本研究中，我们利用口服感染HTLV-1且对病毒抗原（如Gag和Env）无抗体反应的大鼠建立了一个母婴传播模型。在这个模型中，HTLV-1可以以很高的比率（50%-100%）从感染的母鼠传播给它们的后代，母婴传播率往往与感染母鼠的PVL相关。此外，用大鼠抗HTLV-1 Env gp46中和单克隆抗体对未感染的成年大鼠和感染的母鼠进行被动免疫，分别无法抑制成年大鼠的原发性口服HTLV-1感染和HTLV-1向后代的垂直传播。我们的研究结果表明，这个母婴传播模型不仅有助于研究母婴传播的机制，还有助于研究抗HTLV-1抗体在HTLV-1母婴传播中的作用。它们还提供了一些关于母体抗体在母婴传播中的作用的信息，在设计预防HTLV-1母婴传播的策略时应予以考虑。
