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 immunodefi- ciency virus (HIV), Ebola, dengue, cytomegalovirus, and hepatitis C, possess glycans that recognize C-type lectins, espe- cially 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 no- rovirus infections, respectively; human milk oligosaccharides (HMOs) could block enterovirus 71 and norovirus infec- tions. 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 im- prove 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.