Breast milk-derived factors (especially, lactoferrin and TGF-β) and milk-borne retroviruses

转化生长因子-β在HIV-1感染中的作用转化生长因子-β介导的对HIV-1感染的不同作用，取决于细胞类型。在母乳中发现的3种细胞类型中，转化生长因子-β对乳腺上皮MCF7细胞的感染有抑制作用，对巨噬细胞的感染有增强作用，对淋巴细胞的感染影响不大。转化生长因子-β信号转导了核转录因子-kB途径，导致转录抑制因子启动子在MCF-7细胞和巨噬细胞激活。在MCF-7细胞中，转化生长因子-β对I-kB激酶的诱导起着至关重要的作用。在体内，乳铁蛋白的抗病毒作用已被证明在体外可以抑制多种病毒的感染，但其有效性在体内很少得到证实。因此，我们在托儿所和幼儿园调查口服乳铁蛋白是否可以预防或改善轮状病毒胃肠炎。我们已经证明乳铁蛋白对轮状病毒胃肠炎的发病率几乎没有影响，但显著降低了疾病的严重程度。HTLV-I税务诱导乳铁蛋白表达乳铁蛋白乳铁蛋白来自乳腺上皮和中性粒细胞。我们已证实乳腺上皮细胞MCF-7或中性粒细胞分化的HL-60细胞与HTLV-I感染的MT-2细胞共培养可诱导乳铁蛋白基因的表达。这种作用可被无细胞MT-2培养上清液或重组HTLV-I Tax蛋白取代。我们还证明了Tax可以反式激活乳铁蛋白启动子。结合我们以前的研究表明乳铁蛋白可以反式激活HTLV-I LTR启动子，乳铁蛋白和HTLV-I Tax之间的相互作用可能在该病毒的乳源性传播中发挥重要作用。

Effect of TGF-β on HIV-1 InfectionTGF-β mediated differential effect on HIV-1 infection, depending on cell types. Among 3 cell types found in breast milk, TGF-β suppressed HIV-1 infection of mammary epithelial MCF-7 cells, enhanced that of macrophages, and had little effect on that of lymphocytes. TGF-β signaled NF-kB pathway, resulting in transcriptional repression of LTR promoter in MCF-7 cells and activation in macrophages. In MCF-7 cells, TGF-β induction of I-kB kinase played a critical role.In Vivo Antiviral Effect of LactoferrinLactoferrin has been shown to inhibit in vitro infection with a number of viruses ; however, its efficacy has rarely been confirmed in vivo. Therefore, we investigated whether orally administered lactoferrin could prevent or ameliorate rotaviral gastroenteritis in nurseries and kindergartens. We have demonstrated that lactoferrin had little effect on incidence of rotaviral gastroenteritis, but significantly reduced severity of disease.HTLV-I Tax Induction of Lactoferrin ExpressionLactoferrin in breast mile is derived from mammary epithelium and neutrophils. We have demonstrated that lactoferrin gene expression was induced by co-culture of mammary epithelial MCF-7 cells or neutrophil-differentiated HL-60 cells with HTLV-I-infected MT-2 cells. Such effect could be replaced with cell-free MT-2 culture supernatants or recombinant HTLV-I Tax protein. We have also demonstrated that Tax could transactivate lactoferrin promoter. Taken together with our previous study demonstrating that lactoferrin can transactivate HTLV-I LTR promoter, mutual interaction between lactoferrin and HTLV-I Tax may play an important role in milk-borne transmission of this virus.