Protection from Viral Infections by Human Milk Oligosaccharides: Direct Blockade and Indirect Modulation of Intestinal Ecology and Immune Reactions

Sugar-lectin interactions play an important role in viral infections. Many viruses, such as human immunodeficiency virus (HIV), Ebola, dengue, cytomegalovirus, and hepatitis C, possess glycans that recognize C-type lectins, especially CD209 (DC-SIGN), for infection. Other viruses possess lectins on their surfaces that recognize glycan epitopes on human epithelial cells for infection. Human and avian influenza viruses recognize different glycan epitopes, sialic acid-2,6 galactose (SA-2,6Gal) and SA-2,3Gal, respectively, as their receptors, resulting in different host ranges for these two viruses. We and others have shown that sialogalactosides and fucosyllactoses are receptors for enterovirus 71 and norovirus infections, respectively; human milk oligosaccharides (HMOs) could block enterovirus 71 and norovirus infections. Several lines of evidence also suggest that HMOs cannot only mimic viral receptors and block viral infections, but also raise immune responses through sugar/lectin (galactosides/galactins and sialylglycans/Siglecs) interactions and improve gut ecology by nurturing intestinal cells and/or intestinal microbiota. This review article summarizes how and why HMOs directly or indirectly protect humans from viral infections.