Functional genetic variants in DC-SIGNR are associated with mother-to-child transmission of HIV-1.
Functional genetic variants in DC-SIGNR are associated with mother-to-child transmission of HIV-1.
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DOI：
10.1371/journal.pone.0007211
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发表时间：
2009-10-07
期刊：
影响因子：
3.7
通讯作者：
Roger M
中科院分区：
文献类型：
--
作者：
Boily-Larouche G;Iscache AL;Zijenah LS;Humphrey JH;Mouland AJ;Ward BJ;Roger M
母婴传播（MTCT）是全球儿童感染HIV-1的主要原因。鉴于C型凝集素受体，树突状细胞特异性ICAM-抓取非整合素相关（DC-SIGNR，也称为CD 209 L或肝/淋巴结特异性ICAM-抓取非整合素（L-SIGN）），可以与包括HIV-1在内的病原体相互作用，并在母胎界面表达，我们假设它可能影响HIV-1的MTCT。为了研究DC-SIGNR在HIV-1母婴传播中的潜在作用，我们在津巴布韦哈拉雷招募的197名HIV感染母亲及其婴儿的一个特征良好的队列中进行了DC-SIGNR的遗传关联研究。在调整了一些母体因素后，携带两个DC-SIGNR H1和/或H3单倍型（H1-H1、H1-H3、H3-H3）拷贝的婴儿宫内（IU）HIV-1感染风险增加3.6倍（P = 0.013），分娩期（IP）HIV-1感染风险增加5.7倍（P =0.025）。 H1和H3单倍型在启动子区（p-198 A）和内含子2（int 2 - 180 A）共有两个单核苷酸多态性（SNP），与IU（P = 0.045和P = 0.003，分别）和IP（P = 0.025，int 2 - 180 A）HIV-1感染的风险增加相关。 启动子变体在体外降低转录活性。在携带p-198 A和int 2 - 180 A突变的纯合子H1婴儿中，我们观察到胎盘DC-SIGNR转录物水平降低4倍，与非携带者婴儿相比，不成比例地影响膜结合亚型的表达（P = 0.011）。 这些结果表明，DC-SIGNR在HIV-1的母婴传播中起着至关重要的作用，受损的胎盘DC-SIGNR表达增加了传播的风险。
Mother-to-child transmission (MTCT) is the main cause of HIV-1 infection in children worldwide. Given that the C-type lectin receptor, dendritic cell-specific ICAM-grabbing non-integrin-related (DC-SIGNR, also known as CD209L or liver/lymph node–specific ICAM-grabbing non-integrin (L-SIGN)), can interact with pathogens including HIV-1 and is expressed at the maternal-fetal interface, we hypothesized that it could influence MTCT of HIV-1. To investigate the potential role of DC-SIGNR in MTCT of HIV-1, we carried out a genetic association study of DC-SIGNR in a well-characterized cohort of 197 HIV-infected mothers and their infants recruited in Harare, Zimbabwe. Infants harbouring two copies of DC-SIGNR H1 and/or H3 haplotypes (H1-H1, H1-H3, H3-H3) had a 3.6-fold increased risk of in utero (IU) (P = 0.013) HIV-1 infection and a 5.7-fold increased risk of intrapartum (IP) (P = 0.025) HIV-1 infection after adjusting for a number of maternal factors. The implicated H1 and H3 haplotypes share two single nucleotide polymorphisms (SNPs) in promoter region (p-198A) and intron 2 (int2-180A) that were associated with increased risk of both IU (P = 0.045 and P = 0.003, respectively) and IP (P = 0.025, for int2-180A) HIV-1 infection. The promoter variant reduced transcriptional activity in vitro. In homozygous H1 infants bearing both the p-198A and int2-180A mutations, we observed a 4-fold decrease in the level of placental DC-SIGNR transcripts, disproportionately affecting the expression of membrane-bound isoforms compared to infant noncarriers (P = 0.011). These results suggest that DC-SIGNR plays a crucial role in MTCT of HIV-1 and that impaired placental DC-SIGNR expression increases risk of transmission.
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影响因子：
30.8
作者：
Chan VS;Chan KY;Chen Y;Poon LL;Cheung AN;Zheng B;Chan KH;Mak W;Ngan HY;Xu X;Screaton G;Tam PK;Austyn JM;Chan LC;Yip SP;Peiris M;Khoo US;Lin CL
通讯作者：
Lin CL
影响因子：
2.7
作者：
Boily-Larouche G;Zijenah LS;Mbizvo M;Ward BJ;Roger M
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影响因子：
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作者：
Snyder, GA;Ford, J;Sun, PD
通讯作者：
Sun, PD
DOI：
10.1073/pnas.051631398
发表时间：
2001-02-27
影响因子：
11.1
作者：
Pöhlmann, S;Soilleux, EJ;Doms, RW
通讯作者：
Doms, RW
影响因子：
15.8
作者：
Kwiek, JJ;Mwapasa, V;Meshnick, SR
通讯作者：
Meshnick, SR