TY - JOUR
T1 - Human milk inhibits some enveloped virus infections, including SARS-CoV-2, in an intestinal model
AU - Aknouch, Ikrame
AU - Sridhar, Adithya
AU - Freeze, Eline
AU - Giugliano, Francesca Paola
AU - van Keulen, Britt J.
AU - Romijn, Michelle
AU - Calitz, Carlemi
AU - García-Rodríguez, Inés
AU - Mulder, Lance
AU - Wildenberg, Manon E.
AU - Muncan, Vanesa
AU - van Gils, Marit J.
AU - van Goudoever, Johannes B.
AU - Stittelaar, Koert J.
AU - Wolthers, Katja C.
AU - Pajkrt, Dasja
N1 - Funding Information: HIS mouse facility (Amsterdam UMC, The Netherlands) is acknowledged for providing fetal tissues. The authors would like to thank Dr. Kees Weijer, Mrs. Esther Siteur-van Rijnstra, Mrs. Cynthia A van der Linden, and Dr. Arie Voordouw for facilitating the provision of the fetal material. Cellular Imaging core facility of the Amsterdam UMC, The Netherlands is acknowledged for the advanced light microscopy. The authors also wish to thank Jonneke de Rijck, Guido van der Net, and Lie Mulder from Viroclinics Xplore, Gerrit Koen, Hetty van Eijk, and Thomas J Roodsant from the Department of Medical Microbiology, Amsterdam UMC, Jacqueline Vermeulen from the Tytgat Institute, Amsterdam UMC, and Daisy I Picavet-Havik and Ron A Hoebe from the Cellular Imaging core facility, Amsterdam UMC for their technical support. This work was funded under the OrganoVIR project (grant 812673) and GUTVIBRATIONS (grant 953201) in the European Union’s Horizon 2020 programme, the PPP allowance made available by Health~Holland, Top Sector Life Sciences and Health, to Amsterdam UMC, location Academic Medical Center to stimulate public-private partnerships, and funding from Stichting Steun Emma Kinderziekenhuis. The funders had no role in the design of the study, data analysis, writing of the manuscript, or in the decision to publish the results. Publisher Copyright: © 2022 Aknouch et al.
PY - 2022/12/1
Y1 - 2022/12/1
N2 - Human milk is important for antimicrobial defense in infants and has well demonstrated antiviral activity. We evaluated the protective ability of human milk against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a human fetal intestinal cell culture model. We found that, in this model, human milk blocks SARS-CoV-2 replication, irrespective of the presence of SARS-CoV-2 spike-specific antibodies. Complete inhibition of both enveloped Middle East respiratory syndrome coronavirus and human respiratory syncytial virus infections was also observed, whereas no inhibition of non-enveloped enterovirus A71 infection was seen. Transcriptome analysis after 24 h of the intestinal monolayers treated with human milk showed large transcriptomic changes from human milk treatment, and subsequent analysis suggested that ATP1A1 down-regulation by milk might be of importance. Inhibition of ATP1A1 blocked SARS-CoV-2 infection in our intestinal model, whereas no effect on EV-A71 infection was seen. Our data indicate that human milk has potent antiviral activity against particular (enveloped) viruses by potentially blocking the ATP1A1-mediated endocytic process.
AB - Human milk is important for antimicrobial defense in infants and has well demonstrated antiviral activity. We evaluated the protective ability of human milk against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a human fetal intestinal cell culture model. We found that, in this model, human milk blocks SARS-CoV-2 replication, irrespective of the presence of SARS-CoV-2 spike-specific antibodies. Complete inhibition of both enveloped Middle East respiratory syndrome coronavirus and human respiratory syncytial virus infections was also observed, whereas no inhibition of non-enveloped enterovirus A71 infection was seen. Transcriptome analysis after 24 h of the intestinal monolayers treated with human milk showed large transcriptomic changes from human milk treatment, and subsequent analysis suggested that ATP1A1 down-regulation by milk might be of importance. Inhibition of ATP1A1 blocked SARS-CoV-2 infection in our intestinal model, whereas no effect on EV-A71 infection was seen. Our data indicate that human milk has potent antiviral activity against particular (enveloped) viruses by potentially blocking the ATP1A1-mediated endocytic process.
UR - http://www.scopus.com/inward/record.url?scp=85135435306&partnerID=8YFLogxK
U2 - https://doi.org/10.26508/lsa.202201432
DO - https://doi.org/10.26508/lsa.202201432
M3 - Article
C2 - 35926873
SN - 2575-1077
VL - 5
JO - Life Science Alliance
JF - Life Science Alliance
IS - 12
M1 - e202201432
ER -