Immunoglobulin A Targeting on the N-Terminal Moiety of Viral Phosphoprotein Prevents Measles Virus from Evading Interferon-β Signaling.

Immunoglobulin A (IgA) can inhibit intracellular viral replication during its transport across the epithelial cells. We find a monoclonal IgA antibody 7F1-IgA against the N-terminal moiety of the phosphoprotein (PNT) of measles virus (MV), which inhibits the intracellular replication of MV in Caco-2 cells but not in interferon-deficient Vero-pIgR cells. Transcytosis of 7F1-IgA across the MV-infected Caco-2 cells enhances the production of interferon-β (IFN-β) and the expression of IFN-stimulated genes, rendering Caco-2 cells with higher antiviral immunity. 7F1-IgA specifically interacts with MV phosphoprotein inside the MV-infected Caco-2 cell and prevents MV phosphoprotein from inhibiting the phosphorylation of JAK1 and STAT1. The intraepithelial interaction between 7F1-IgA and the viral phosphoprotein results in an earlier and stronger phosphorylation of JAK1 and STAT1 and, consequently, a more efficient nuclear translocation of STAT1 for the activation of the type I interferon pathway. Thus, IgA against phosphoprotein prevents a virus from evading type I IFN signaling and confers host epithelial cells efficient innate antiviral immunity, which potentiates a new antiviral target and an antiviral strategy.