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

来源：

CELLS | 2025年 / 14卷 / 04期

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.

引用

页数：15

共 55 条

[41]

Guo M.M., Zhang K., Zhang J.H., Human Breast Milk-Derived Exosomal miR-148a-3p Protects Against Necrotizing Enterocolitis by Regulating p53 and Sirtuin 1, Inflammation, 45, pp. 1254-1268, (2022)

[42]

Zheng J., Yang T., Gao S., Cheng M., Shao Y., Xi Y., Guo L., Zhang D., Gao W., Zhang G., Et al., miR-148a-3p silences the CANX/MHC-I pathway and impairs CD8(+) T cell-mediated immune attack in colorectal cancer, FASEB J, 35, (2021)

[43]

Yu Y., Du L., Zhang J., Febrile Seizure-Related miR-148a-3p Exerts Neuroprotection by Promoting the Proliferation of Hippocampal Neurons in Children with Temporal Lobe Epilepsy, Dev. Neurosci, 43, pp. 312-320, (2021)

[44]

Huang Y., Wang Y., Liu X., Ouyang Y., Silencing lncRNA HOTAIR improves the recovery of neurological function in ischemic stroke via the miR-148a-3p/KLF6 axis, Brain Res. Bull, 176, pp. 43-53, (2021)

[45]

Elsarraj H.S., Hong Y., Valdez K., Carletti M., Salah S.M., Raimo M., Taverna D., Prochasson P., Bharadwaj U., Tweardy D.J., Et al., A novel role of microRNA146b in promoting mammary alveolar progenitor cell maintenance, J. Cell Sci, 126, pp. 2446-2458, (2013)

[46]

Lee H.M., Kim T.S., Jo E.K., MiR-146 and miR-125 in the regulation of innate immunity and inflammation, BMB Rep, 49, pp. 311-318, (2016)

[47]

Paterson M.R., Kriegel A.J., MiR-146a/b: A family with shared seeds and different roots, Physiol. Genom, 49, pp. 243-252, (2017)

[48]

Zempleni J., Sukreet S., Zhou F., Wu D., Mutai E., Milk-Derived Exosomes and Metabolic Regulation, Annu. Rev. Anim. Biosci, 7, pp. 245-262, (2019)

[49]

Naslund T.I., Paquin-Proulx D., Paredes P.T., Vallhov H., Sandberg J.K., Gabrielsson S., Exosomes from breast milk inhibit HIV-1 infection of dendritic cells and subsequent viral transfer to CD4+ T cells, AIDS, 28, pp. 171-180, (2014)

[50]

Civra A., Francese R., Donalisio M., Tonetto P., Coscia A., Sottemano S., Balestrini R., Faccio A., Cavallarin L., Moro G.E., Et al., Human Colostrum and Derived Extracellular Vesicles Prevent Infection by Human Rotavirus and Respiratory Syncytial Virus in Vitro, J. Hum. Lact, 37, pp. 122-134, (2021)

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