Meddows-Taylor Stephen, Donninger Samantha L, Paximadis Maria, Schramm Diana B, Anthony Fiona S, Gray Glenda E, Kuhn Louise, Tiemessen Caroline T
AIDS Virus Research Unit, National Institute for Communicable Diseases, and Department of Virology, University of the Witwatersrand, Private Bag X4, Sandringham, Johannesburg 2131, South Africa.
Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, Soweto, South Africa.
J Gen Virol. 2006 Jul;87(Pt 7):2055-2065. doi: 10.1099/vir.0.81709-0.
The role of CC chemokines in protection against mother-to-child human immunodeficiency virus type 1 (HIV-1) transmission is not well understood. It was observed that mitogen-induced production of CCL3 and CCL4 by cord-blood mononuclear cells was increased among infants born to HIV-positive compared with HIV-negative mothers, and that a deficiency in production of CCL3 was associated with increased susceptibility to intrapartum HIV-1 infection. CCL3-L1 gene copy number was associated with CCL3 production and with vertical transmission. However, at equivalent CCL3-L1 gene copy numbers, infants who acquired HIV-1 infection relative to their exposed but uninfected counterparts had lower production of CCL3, suggesting that they may harbour some non-functional copies of this gene. Nucleotide changes that may influence CCL3 production were evident in the CCL3 and CCL3-L1 genes upstream of exon 2. Our findings suggest that infants who display a deficient-production phenotype of CCL3 are at increased risk of acquiring HIV-1, indicating that this chemokine in particular plays an essential role in protective immunity.
CC趋化因子在预防母婴1型人类免疫缺陷病毒（HIV-1）传播中的作用尚未完全明确。研究发现，与HIV阴性母亲所生婴儿相比，HIV阳性母亲所生婴儿脐带血单个核细胞经丝裂原诱导产生的CCL3和CCL4增加，且CCL3产生不足与分娩期HIV-1感染易感性增加有关。CCL3-L1基因拷贝数与CCL3产生及垂直传播相关。然而，在CCL3-L1基因拷贝数相同的情况下，感染HIV-1的婴儿相较于暴露但未感染的婴儿，CCL3产生量更低，这表明他们可能携带该基因的一些无功能拷贝。在外显子2上游的CCL3和CCL3-L1基因中，可明显看到可能影响CCL3产生的核苷酸变化。我们的研究结果表明，表现出CCL3产生不足表型的婴儿感染HIV-1的风险增加，这表明该趋化因子在保护性免疫中尤其起着至关重要的作用。
