PT - JOURNAL ARTICLE 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 TI - Human milk inhibits some enveloped virus infections, including SARS-CoV-2, in an intestinal model AID - 10.26508/lsa.202201432 DP - 2022 Dec 01 TA - Life Science Alliance PG - e202201432 VI - 5 IP - 12 4099 - https://www.life-science-alliance.org/content/5/12/e202201432.short 4100 - https://www.life-science-alliance.org/content/5/12/e202201432.full SO - Life Sci. Alliance2022 Dec 01; 5 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.