Kramer Evelien, Patil Ketki, Triantis Vassilis, Bastiaans Jan A H, Mazzon Michela, Ramani Sasirekha, Lambers Tim T
FrieslandCampina, Amersfoort, Netherlands.
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, United States.
Front Nutr. 2024 Jul 31;11:1416352. doi: 10.3389/fnut.2024.1416352. eCollection 2024.
Among the most common mucosal viral infections in infants are rotavirus, one of the main causes of severe gastroenteritis in infants and children up to 5 years, and respiratory syncytial virus (RSV), one of the leading causes of lower respiratory tract infections. Both human milk and bovine milk derived factors may provide protection against mucosal viral infections. More recently, a similar activity of milk derived proteins was suggested for SARS-CoV-2. The goal of the current study was to test antiviral activity of the bovine milkfat globule membrane (MFGM) against rotavirus, RSV and SARS-CoV-2 and to further characterize MFGM-enriched whey to identify which components in MFGM-enriched whey may contribute to the inhibitory activity.
The effects of MFGM-enriched whey, its whey protein isolate counterpart (WPI, obtained from the same production process) and a conventional whey protein concentrate (WPC) on rotavirus (strains Wa and SA114F), RSV (strain RSV-A2) and SARS-CoV-2 (Alpha variant) infectivity were determined using MA104 cells, human alveolar basal epithelial (A549) cells and monkey kidney (Vero E6) cells, respectively. The compounds were characterized in detail by LC-MS/MS and P-NMR to determine protein and phospholipid composition, respectively.
Relative to its WPI counterpart, MFGM-enriched whey demonstrated a dose-dependent inhibition for both rotavirus and RSV whereas for SARS-CoV-2 inhibition was only observed at the highest concentration tested. Label-free quantification (LFQ) and intensity based absolute quantification (iBAQ) of identified proteins revealed a clear difference between MFGM-enriched whey and its controls including enrichment of known MFGM proteins and non-MFGM proteins that are enriched simultaneously, some of which have previously been demonstrated to display anti-viral activity. Although not completely absent from other whey protein preparations, MFGM-enriched whey had the highest specific and total phospholipid levels.
MFGM-enriched whey displayed antiviral activity against multiple viruses of clinical importance. This study provides insights into the active components in MFGM-enriched whey and may contribute to previous clinical observations with MFGM-enriched formula demonstrating reduced respiratory and gastrointestinal infections in formula fed infants.
在婴儿最常见的黏膜病毒感染中，轮状病毒是5岁以下婴幼儿严重肠胃炎的主要病因之一，呼吸道合胞病毒（RSV）是下呼吸道感染的主要病因之一。人乳和牛乳衍生因子均可提供针对黏膜病毒感染的保护作用。最近，有人提出牛乳衍生蛋白对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）具有类似活性。本研究的目的是测试牛乳脂肪球膜（MFGM）对轮状病毒、RSV和SARS-CoV-2的抗病毒活性，并进一步表征富含MFGM的乳清，以确定富含MFGM的乳清中的哪些成分可能有助于抑制活性。
分别使用MA104细胞、人肺泡基底上皮（A549）细胞和猴肾（Vero E6）细胞，测定富含MFGM的乳清、其乳清蛋白分离物对应物（WPI，来自相同生产过程）和传统乳清蛋白浓缩物（WPC）对轮状病毒（Wa株和SA114F株）、RSV（RSV-A2株）和SARS-CoV-2（Alpha变异株）感染性的影响。分别通过液相色谱-串联质谱（LC-MS/MS）和磷核磁共振（P-NMR）详细表征化合物，以确定蛋白质和磷脂组成。
相对于其WPI对应物，富含MFGM的乳清对轮状病毒和RSV均表现出剂量依赖性抑制作用，而对于SARS-CoV-2，仅在测试的最高浓度下观察到抑制作用。对鉴定出的蛋白质进行无标记定量（LFQ）和基于强度的绝对定量（iBAQ），结果显示富含MFGM的乳清与其对照之间存在明显差异，包括已知MFGM蛋白和同时富集的非MFGM蛋白的富集情况，其中一些蛋白先前已被证明具有抗病毒活性。虽然其他乳清蛋白制剂中并非完全没有，但富含MFGM的乳清具有最高的特定磷脂水平和总磷脂水平。
富含MFGM的乳清对多种具有临床重要性的病毒具有抗病毒活性。本研究深入了解了富含MFGM的乳清中的活性成分，并可能有助于先前关于富含MFGM的配方奶粉可降低配方奶喂养婴儿呼吸道和胃肠道感染的临床观察结果。
