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

TGF-β对HIV-1抑制的作用TGF-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，TGF-β抑制乳腺上皮MCF-7细胞的HIV-1感染，增强巨噬细胞的HIV-1感染，而对淋巴细胞的HIV-1感染几乎没有影响。TGF-β信号传导NF-kB通路，导致MCF-7细胞中LTR启动子的转录抑制和巨噬细胞中的激活。在MCF-7细胞中，TGF-β诱导的I-kB激酶发挥了关键作用。乳铁蛋白的体内抗病毒作用乳铁蛋白在体外可抑制多种病毒的感染，但在体内的疗效很少得到证实。因此，我们调查口服乳铁蛋白是否可以预防或改善托儿所和幼儿园的轮状病毒胃肠炎。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，但显着降低疾病的严重程度。HTLV-Ⅰ税诱导乳铁蛋白的表达乳铁蛋白在乳房英里是来自乳腺上皮细胞和中性粒细胞。我们已经证明，乳铁蛋白基因的表达诱导乳腺上皮MCF-7细胞或嗜中性粒细胞分化的HL-60细胞与HTLV-I感染的MT-2细胞的共培养。这种作用可以用无细胞MT-2培养上清液或重组HTLV-1 Tax蛋白代替。我们还证明了Tax可以反式激活乳铁蛋白启动子。结合我们先前的研究表明，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.