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IgA targeting on the &agr;‐molecular recognition element (&agr;‐MoRE) of viral phosphoprotein inhibits measles virus replication by interrupting formation and function of P‐N complex intracellularly

ABSTRACT Secretory IgA (SIgA) antibody is unique for its capability to transit through epithelial cells by transcytosis and thus has opportunities and probabilities to interact with all viral components during… Click to show full abstract

ABSTRACT Secretory IgA (SIgA) antibody is unique for its capability to transit through epithelial cells by transcytosis and thus has opportunities and probabilities to interact with all viral components during viral replication which may result in the inhibition of viral replication intracellularly. Here, we report a novel IgA mAb 1D11‐IgA against phosphoprotein (P) of measles virus (MV), which is able to interact specifically with P in MV infected Vero‐pIgR cells grown in a two‐chamber transwell system. The binding epitope of 1D11‐IgA involves a key residue proline 23 in P protein, which is among the &agr;‐molecular recognition element (&agr;‐MoRE) of P and critical for N0‐P complex. The antibody appears to block P to interact with N in P‐N complex and thus may inhibit the function of viral RdRp complex, which results in decreased synthesis of viral genome RNA and mRNA. Our data together demonstrate that IgA is able to interact with viral phosphoprotein intraepithelial cells and neutralize viral replication by interrupting formation of P‐N complex and function of RdRp. The findings highlight that IgA has a unique anti‐viral activity by targeting viral conserved components critical for viral replication, which serves as a proof‐of‐concept assessment of the druggability of mononegavirales P‐N interfaces. HIGHLIGHTSA novel IgA mAb 1D11‐IgA targeting on the &agr;‐MoRE of viral phosphoprotein inhibits measles virus replication intracellularly.The 1D11‐IgA inhibits measles virus replication by interrupting P‐N complex formation during its transcytosis.The study highlights the &agr;‐MoRE of P is a very specific and promising antiviral target for antiviral drug screen.

Keywords: replication interrupting; inhibits measles; viral phosphoprotein; replication; measles virus

Journal Title: Antiviral Research
Year Published: 2019

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