Prenatal SARS-CoV-2 Infection Alters Human Milk-Derived Extracellular Vesicles

被引:1
作者
Chutipongtanate, Somchai [1 ]
Kongsomros, Supasek [1 ,2 ]
Cetinkaya, Hatice [1 ]
Zhang, Xiang [1 ]
Kuhnell, Damaris [1 ]
Benefield, Desiree [3 ]
Haffey, Wendy D. [4 ]
Wyder, Michael A. [4 ]
Kwatra, Gaurav [5 ,6 ]
Conrey, Shannon C. [1 ]
Burrell, Allison R. [5 ]
Langevin, Scott M. [7 ]
Esfandiari, Leyla [2 ]
Newburg, David S. [1 ]
Greis, Kenneth D. [4 ]
Staat, Mary A. [5 ]
Morrow, Ardythe L. [1 ,5 ]
机构
[1] Univ Cincinnati, Dept Environm & Publ Hlth Sci, Coll Med, Cincinnati, OH 45267 USA
[2] Univ Cincinnati, Dept Biomed Engn, Cincinnati, OH 45267 USA
[3] Univ Cincinnati, Ctr Adv Struct Biol, Dept Mol & Cellular Biosci, Coll Med, Cincinnati, OH 45267 USA
[4] Univ Cincinnati, Dept Canc Biol, Coll Med, Cincinnati, OH 45267 USA
[5] Cincinnati Childrens Hosp, Dept Infect Dis, Med Ctr, Cincinnati, OH 45267 USA
[6] Christian Med Coll & Hosp, Dept Clin Microbiol, Vellore 632004, India
[7] Univ Vermont, Larner Coll Med, Burlington, VT 05405 USA
基金
美国国家卫生研究院;
关键词
COVID-19; exosomes; human milk; microRNAs; proteomics; PROTEOMIC ANALYSIS; BREAST-MILK; EXOSOMES; BOVINE; COLOSTRUM; CELLS;
D O I
10.3390/cells14040284
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Human milk-derived extracellular vesicles (HMEVs) are key components in breast milk, promoting infant health and development. Maternal conditions could affect HMEV cargo; however, the impact of SARS-CoV-2 infection on HMEVs remains unknown. This study investigated the influence of SARS-CoV-2 infection during pregnancy on postpartum HMEV molecules. The median duration from SARS-CoV-2 test positivity to milk collection was 3 months. After defatting and casein micelle disaggregation, HMEVs were isolated from milk samples of nine mothers with prenatal SARS-CoV-2 and six controls by sequential centrifugation, ultrafiltration, and qEV-size exclusion chromatography. The presence of HMEV was confirmed via transmission electron microscopy. Nanoparticle tracking analysis demonstrated particle diameters of <200 nm and yields of >1 x 10(11) particles per mL of milk. Western immunoblots detected ALIX, CD9, and HSP70, supporting the presence of HMEVs in the isolates. Cargo from thousands of HMEVs were analyzed using a multi-omics approach, including proteomics and microRNA sequencing, and predicted that mothers with prenatal SARS-CoV-2 infection produced HMEVs with enhanced functionalities involving metabolic reprogramming, mucosal tissue development, and immunomodulation. Our findings suggest that SARS-CoV-2 infection during pregnancy boosts mucosal site-specific functions of HMEVs, potentially protecting infants against viral infections. Further prospective studies should be pursued to reevaluate the short- and long-term benefits of breastfeeding in the post-COVID era.
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页数:15
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