Protection against hepatitis C and other enveloped viruses? Another reason why "breast is best".
Protection against hepatitis C and other enveloped viruses? Another reason why "breast is best".
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预防丙型肝炎和其他包膜病毒？
DOI：
10.1093/infdis/jit521
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发表时间：
2013
期刊：
影响因子：
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通讯作者：
Jhaveri,Ravi
中科院分区：
文献类型：
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作者：
Jhaveri,Ravi
美国的母乳喂养率一直在稳步上升，1971 年母乳喂养率为 30%，母乳喂养持续 6 个月为 5%–10%，2003 年分别为 70% 和 30%，2009 年分别为 77% 和 47% [1–3]。这些数字还包括不完全母乳喂养且仍未达到 HealthyPeople 2020 国家目标（即 80% 开始母乳喂养和 6 个月时母乳喂养 60%）的母亲[3]。 2012 年，美国儿科学会重申其建议，即婴儿在 6 个月大之前应纯母乳喂养，并持续至少 1 岁并开始添加固体食物 [1]。母乳喂养的许多好处长期以来一直被吹捧：它是“天然”的选择，与配方奶相比，母乳的营养成分更容易被婴儿的消化系统吸收，母乳喂养增强了母婴情感纽带，母乳对婴儿的微生物组产生了有益的影响，包括引入益生菌样生物体[1,2,4]，并且母乳可以排除传染源。工业化国家和发展中国家长期以来都认为母乳喂养可以保护婴儿免受呼吸道和腹泻疾病的影响 [1, 2]。这种益处是如此强大，以至于超过了资源匮乏地区受感染的母亲所生的婴儿可能感染人类免疫缺陷病毒 (HIV) 的风险 [5]。长期以来，这种保护的原因归因于乳汁中的母体抗体以及母体淋巴细胞，它们也能提供针对各种传染源的保护[6, 7]。其他牛奶成分，如乳铁蛋白，也已被证明具有抗菌特性，可提供额外的保护 [8]。在本期杂志中，Pfaender 等人发现了一种新机制，母乳可以通过该机制保护婴儿免受丙型肝炎病毒 (HCV；[9]) 等包膜病毒的侵害。众所周知，HCV 是成人肝病的主要原因[10]。 HCV 的血源性和垂直传播众所周知，但对其他传播方式知之甚少 [10, 11]。 20 世纪 90 年代的几项研究报告了母乳喂养传播 HCV [12-14]。在这些研究中，母乳中检测到的 HCV 浓度比血清浓度低 3-4 个对数级 [13]。一项研究宣称母乳是感染婴儿的传播源，但该研究使用的感染标准可能表明垂直获得的病毒[12]。尚无具体证据证明母乳喂养确实会传播 HCV，而且美国疾病控制与预防中心和美国肝病研究协会均不反对 HCV 感染女性的这种做法，除非她们乳头破裂或出血 [10]。没有传播的原因可归因于上面列出的许多原因：母体抗体、母体 HCV 特异性淋巴细胞、HCV 水平极低，或者病毒可能不以其最具传染性的形式存在（与低密度脂蛋白复合的病毒）。直到 Pfaender 等人发表文章 [9] 之前，还没有具体的研究充分研究了所涉及的保护机制。在这篇文章中，作者设计了一个体外系统来研究母乳中和 HCV 细胞培养病毒 JFH1 感染性的能力 [9]。他们首先表明，冷冻等分母乳可将 JFH1 的病毒感染性抑制 2-3 个对数级。在系统测试母乳并显示不干扰 RNA 复制或衣壳蛋白产生后，
Breastfeeding rates in the United States have been steadily increasing from rates of 30% initiation and 5%–10% continuing through 6 months in 1971, 70% and 30%, respectively, in 2003 and 77% and 47% in 2009 [1–3]. These numbers also include mothers who are not exclusively breastfeeding and still fall short of HealthyPeople 2020 national goals of 80% initiation and 60% breastfeeding at 6 months [3]. In 2012, the American Academy of Pediatrics reaffirmed its recommendation that infants be exclusively breastfed until 6 months of age with continuation through at least 1 year as solid foods are introduced [1]. The many benefits of breastfeeding have long been touted: it is the “natural” option, the nutritional content of breast milk is more easily absorbed by the infant’s digestive system compared to formulas, breastfeeding enhances the mother-infant emotional bond, breast milk provides beneficial effects on the infant’s microbiome, including the introduction of probiotic-like organisms [1, 2, 4], and breast milk may exclude infectious agents. It has long been accepted in both the industrialized and developing world that breastfeeding protects infants against respiratory and diarrheal illnesses [1, 2]. This benefit is so powerful that it outweighs that possible risk of acquisition of human immunodeficiency virus (HIV) for infants born to infected mothers in resource-poor settings [5]. The reasons for this protection have long been attributed to maternal antibodies within the milk, as well as maternal lymphocytes that also confer protection against various infectious agents [6, 7]. Other milk contents, like lactoferrin, have also been shown to have antimicrobial properties that offer additional protection [8]. In this issue of the Journal, Pfaender et al identify a novel mechanism by which breast milk may protect infants against enveloped viruses such as hepatitis C virus (HCV;[9]). It is widely known that HCV is a major cause of liver disease among adults [10]. The bloodborne and vertical transmission of HCV are well known, but less is known about other modes of transmission [10, 11]. Breastfeeding transmission of HCV was reported in several studies in the 1990’s [12–14]. In these studies, HCV was detected in breast milk at concentrations 3–4 logs lower than serum concentrations [13]. One study declared that breast milk was a source of transmission to an infected infant, but this study used criteria for infection that likely indicated vertically acquired virus [12]. No specific evidence has ever existed for definitive transmission of HCV by breastfeeding, and neither the Centers for Disease Control and Prevention nor the American Association for the Study of Liver Diseases argue against this practice for HCV-infected women unless they have cracked or bleeding nipples [10]. The reasons for the absence of transmission have been attributed to many of those listed above: maternal antibodies, maternal HCV-specific lymphocytes, very low levels of HCV or perhaps that virus does not exist in its most infectious form (virus complexed to lowdensity lipoproteins). No specific studies have adequately investigated the protective mechanisms involved until the article by Pfaender et al [9].In this article, the authors designed an in vitro system to study the ability of breast milk to neutralize the infectivity of the HCV cell culture virus, JFH1 [9]. They first showed that frozen aliquots of breast milk inhibited viral infectivity of JFH1 by 2–3logs. After systematically testing breast milk and showing there was no interference with RNA replication nor with capsid protein production, the