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Immunoglobulin A Targeting on the N‑Terminal Moiety of Viral Phosphoprotein Prevents Measles Virus from Evading Interferon‑β Signaling
journal contribution
posted on 2020-03-11, 12:03 authored by Yi Yang, Dihan Zhou, Bali Zhao, Yuan Cao, Jie Yu, Hu Yan, Wei Zhao, Ejuan Zhang, Jingyi Yang, Maohua Zhong, Qinxue Hu, Li Deng, Huimin YanImmunoglobulin
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.