%0 Journal Article %A Ikrame Aknouch %A Adithya Sridhar %A Eline Freeze %A Francesca Paola Giugliano %A Britt J van Keulen %A Michelle Romijn %A Carlemi Calitz %A Inés García-Rodríguez %A Lance Mulder %A Manon E Wildenberg %A Vanesa Muncan %A Marit J van Gils %A Johannes B van Goudoever %A Koert J Stittelaar %A Katja C Wolthers %A Dasja Pajkrt %T Human milk inhibits some enveloped virus infections, including SARS-CoV-2, in an intestinal model %D 2022 %R 10.26508/lsa.202201432 %J Life Science Alliance %P e202201432 %V 5 %N 12 %X 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. %U https://www.life-science-alliance.org/content/lsa/5/12/e202201432.full.pdf