Glycosylation of Human IgA Directly Inhibits Influenza A and Other Sialic-Acid-Binding Viruses

Highlights

• Heterosubtypic IgA1 or IgA2 antibodies neutralize virus much more potently than IgG1

• Sialic acid in IgA’s C-terminal tail competes with viral receptor binding

• This may represent an innate line of defense against viral pathogens

Summary

Immunoglobulin A (IgA) plays an important role in protecting our mucosal surfaces from viral infection, in maintaining a balance with the commensal bacterial flora, and in extending maternal immunity via breast feeding. Here, we report an additional innate immune effector function of human IgA molecules in that we demonstrate that the C-terminal tail unique to IgA molecules interferes with cell-surface attachment of influenza A and other enveloped viruses that use sialic acid as a receptor. This antiviral activity is mediated by sialic acid found in the complex N-linked glycans at position 459. Antiviral activity was observed even in the absence of classical antibody binding via the antigen binding sites. Our data, therefore, show that the C-terminal tail of IgA subtypes provides an innate line of defense against viruses that use sialic acid as a receptor and the role of neuraminidases present on these virions.