Antibodies directed towards neuraminidase restrict influenza virus replication in primary human bronchial epithelial cells.

Anouk Smet,Tine Ysenbaert,Amanda Gonçalves,Xavier Saelens,Harry Kleanthous,Emma R Job,Joao Paulo Portela Catani,Thorsten U Vogel,Sander Herfst

doi:10.1371/journal.pone.0262873

Abstract

Influenza neuraminidase (NA) is implicated in various aspects of the virus replication cycle and therefore is an attractive target for vaccination and antiviral strategies. Here we investigated the potential for NA-specific antibodies to interfere with A(H1N1)pdm09 replication in primary human airway epithelial (HAE) cells. Mouse polyclonal anti-NA sera and a monoclonal antibody could block initial viral entry into HAE cells as well as egress from the cell surface. NA-specific polyclonal serum also reduced virus replication across multiple rounds of infection. Restriction of virus entry correlated with the ability of the serum or monoclonal antibody to mediate neuraminidase inhibition (NI). Finally, human sera with NI activity against the N1 of A(H1N1)pdm09 could decrease H6N1 virus infection of HAE cells, highlighting the potential contribution of anti-NA antibodies in the control of influenza virus infection in humans.

Highlights

Influenza viruses pose a serious public health threat
Mucins that are present within the mucus layer that lines human airway epithelial (HAE) cells can decrease the entry of influenza viruses into cells [2]
We report that antibodies with neuraminidase inhibition (NI) activity can interfere with the initial round of infection in HAE cells

Summary

Introduction

Influenza viruses pose a serious public health threat. Influenza A and B viruses carry two major surface glycoproteins: hemagglutinin (HA) and neuraminidase (NA). The HA binds to sialic acid present on the surface of target cells. The NA has an opposing function, cleaving the linkage between the sialic acid and the adjacent sugar residue [1]. NA activity aids in virion entry into underlying cells by cleaving sialic acid residues from decoy receptors in the airways [2, 3]. In concert with HA, NA may allow the influenza virion to reach a suitable endocytic patch on the cell surface by promoting a grasping and rolling mechanism [4, 5].

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Conclusion