Virus-Mediated Cell-Cell Fusion.

Héloïse Leroy,Jérôme Bouchet,Marie Woottum,Serge Benichou,Mingyu Han,Maorong Xie,Lucie Bracq

doi:10.3390/ijms21249644

Abstract

Cell-cell fusion between eukaryotic cells is a general process involved in many physiological and pathological conditions, including infections by bacteria, parasites, and viruses. As obligate intracellular pathogens, viruses use intracellular machineries and pathways for efficient replication in their host target cells. Interestingly, certain viruses, and, more especially, enveloped viruses belonging to different viral families and including human pathogens, can mediate cell-cell fusion between infected cells and neighboring non-infected cells. Depending of the cellular environment and tissue organization, this virus-mediated cell-cell fusion leads to the merge of membrane and cytoplasm contents and formation of multinucleated cells, also called syncytia, that can express high amount of viral antigens in tissues and organs of infected hosts. This ability of some viruses to trigger cell-cell fusion between infected cells as virus-donor cells and surrounding non-infected target cells is mainly related to virus-encoded fusion proteins, known as viral fusogens displaying high fusogenic properties, and expressed at the cell surface of the virus-donor cells. Virus-induced cell-cell fusion is then mediated by interactions of these viral fusion proteins with surface molecules or receptors involved in virus entry and expressed on neighboring non-infected cells. Thus, the goal of this review is to give an overview of the different animal virus families, with a more special focus on human pathogens, that can trigger cell-cell fusion.

Highlights

Viruses are acellular organisms in which the genomes consist of RNA or DNA nucleic acid and which obligatory replicate inside host cells
These reports indicate that the fusion protein F plays a central role in human respiratory syncytial virus (HRSV)-mediated syncytium formation, and it was recently suggested that accumulation of the F protein on cell surface of infected cells helped the binding to the plasma membrane of neighboring uninfected cells
Coronaviridae are a family of viruses first characterized in humans in late 1960s which has recently become an increasingly severe threat to global public health, exemplified by the previous outbreaks of Severe Acute Respiratory Syndrome CoV (SARS-CoV) in 2001 and Middle East Respiratory Syndrome CoV (MERS-CoV) in 2012, but especially by the current COVID-19 pandemic induced by SARS-CoV-2 which is responsible for hundreds of thousands of people deaths worldwide [104]

Summary

Introduction

Viruses are acellular organisms in which the genomes consist of RNA or DNA nucleic acid and which obligatory replicate inside host cells. The process generally described for animal virus dissemination between permissive cells is related to release of cell-free viral particles that diffuse from infected cells and subsequently attach and enter new target cells for virus replication. Several distinct mechanisms for virus cell-to-cell transfer and spreading have been described, but some viruses can use the fusogenic capacity of some viral proteins, usually involved in virus entry, expressed at the surface of infected cells to trigger cell-cell fusion between infected virus-donor cells and neighboring target cells to form enlarged multinucleated cells, often called syncytia. Thereby, virus-induced cell-cell fusion and syncytium formation are mainly mediated by specific interactions of certain viral fusion proteins with surface molecules or receptors expressed on neighboring non-infected cells. We will review the data of the literature regarding the main families of animal viruses able to trigger cell-cell fusion, and discuss about the mechanisms of this virus-induced cell-cell fusion process, and how this process could contribute in intercellular virus spread, virulence, and virus persistence

Herpesviridae

Paramyxoviridae

Coronaviridae

Retroviridae

Other Viruses

Concluding Remarks