Human milk inhibits some enveloped virus infections, including SARS-CoV-2, in an intestinal epithelial model by potentially blocking endocytic entry

• DOI: 10.5281/zenodo.5843654
• Publication Date: 2022-01-13
• Authors: Ikrame Aknouch; Adithya Sridhar; Eline Freeze; Francesca Paola G...; Britt van Keulen; Michelle Romijn; Carlemi Calitz; Inés García-Rodrí...; Lance Mulder; Manon E. Wildenberg; Vanesa Muncan; Marit J. van Gils; Johannes Goudoever; Koert J. Stittelaar; Katja C. Wolthers; Dasja Pajkrt
• Keywords: Blocking (statistics)

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 while no inhibition of non-enveloped enterovirus A71 infection was seen. Transcriptome analysis after 24h of the intestinal monolayers treated with human milk showed large transcriptomic changes from human milk treatment and subsequent analysis suggested that ATP1A1 downregulation by milk might be of importance. Inhibition of ATP1A1 blocked SARS-CoV-2 infection in our intestinal model, while 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.<br/>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.<br/>