Rapid and Efficient Cell-to-Cell Transmission of Avian Influenza H5N1 Virus in MDCK Cells Is Achieved by Trogocytosis.

Supasek Kongsomros,Suwimon Manopwisedjaroen,Jarinya Chaopreecha,Arunee Thitithanyanont,Sheng-Fan Wang,Suparerk Borwornpinyo

doi:10.3390/pathogens10040483

Supasek Kongsomros, Suwimon Manopwisedjaroen + Show 4 more

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https://doi.org/10.3390/pathogens10040483

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Journal: Pathogens	Publication Date: Apr 16, 2021
Citations: 8	License type: CC BY 4.0

Affiliation: Mahidol University, Kaohsiung Medical University

Abstract

Viruses have developed direct cell-to-cell transfer strategies to enter target cells without being released to escape host immune responses and antiviral treatments. These strategies are more rapid and efficient than transmission through indirect mechanisms of viral infection between cells. Here, we demonstrate that an H5N1 influenza virus can spread via direct cell-to-cell transfer in Madin-Darby canine kidney (MDCK) cells. We compared cell-to-cell transmission of the H5N1 virus to that of a human influenza H1N1 virus. The H5N1 virus has been found to spread to recipient cells faster than the human influenza H1N1 virus. Additionally, we showed that plasma membrane exchange (trogocytosis) occurs between co-cultured infected donor cells and uninfected recipient cells early point, allowing the intercellular transfer of viral material to recipient cells. Notably, the H5N1 virus induced higher trogocytosis levels than the H1N1 virus, which could explain the faster cell-to-cell transmission rate of H5N1. Importantly, this phenomenon was also observed in A549 human lung epithelial cells, which are representative cells in the natural infection site. Altogether, our results provide evidence demonstrating that trogocytosis could be the additional mechanism utilized by the H5N1 virus for rapid and efficient cell-to-cell transmission.

Highlights

Viral infection occurs when viruses enter target cells and begin to multiply
Some evidence of cell-to-cell transmission has been reported in human influenza viruses [15,16,17], this transmission mode has not been yet studied in the avian influenza H5N1 virus
Madin-Darby canine kidney (MDCK) cells were infected with the H5N1 virus at a multiplicity of infection (MOI) of 1 for 8 h used as donor cells

Summary

Introduction

Viral infection occurs when viruses enter target cells and begin to multiply. New viral particles released from the infected producer cells are transmitted to the target cells. The classical transmission pathway involves the release of the infectious virion into the extracellular fluid for further spread to new target cells via a cell-free infection mechanism [1]. Through the co-evolution of viruses with their host, viruses have developed means for overcoming host barriers and evading host immune defenses, including neutralizing antibodies and antiviral restriction factors. One such evasion tactic involves developing alternative modes of transmission, cell-to-cell viral transfer, in which the virus can hijack cell–cell contact junctions and use them for transmitting viral material to the target cell bypassing diffusion of the virus into the extracellular fluid [1,2,3,4]

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