Virus-Mediated Cell-Cell Fusion

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.

Cell Fusion and Syncytium Formation in Betaherpesvirus Infection

“…Many enveloped viruses belonging to different families of human pathogens mediate cell–cell fusion to enhance viral spread and persistence even in the presence of antiviral effector responses or in the absence of extracellular virions. For example, respiratory viruses such as human respiratory syncytial virus, measles virus, influenza viruses, and SARS-coronaviruses that enter the human body through the epithelial lining of the airways use cell–cell fusion as a strategy to overcome the mucociliary blanket, which contains antibodies and mechanically traps viral particles [ 13 , 14 ]. Thus, cell–cell fusion allows these viruses to spread more efficiently in the lung.…”

Cellular and molecular actors of myeloid cell fusion: podosomes and tunneling nanotubes call the tune

“…This process is mediated by fusogenic proteins of the viral envelopes. During productive infection, the host cell expresses new viral envelope proteins at its plasma membrane, which are able to bind to their receptors on neighboring cells, leading to cell-to-cell fusion and thus virus-induced syncytium formation [56][57][58]. Myeloid cells, particularly macrophages, are an important target for HIV-1, and HIV-1-induced MGC formation is considered a hallmark of macrophage infection.…”

Intervention Strategies for Seasonal and Emerging Respiratory Viruses with Drugs and Vaccines Targeting Viral Surface Glycoproteins

“…Fusion with the host cell membrane then allows the virus to release its genome into the host cell cytoplasm. Viruses create syncytia that involve the host plasma membrane to facilitate cell entry a process leading to conformational changes in their envelope protein [ 41 ]. Very few drugs have been approved for human use that function as envelope protein inhibitors [ 42 ].…”