Drivers and Distribution of Henipavirus-Induced Syncytia: What Do We Know?

Abstract

Syncytium formation, i.e., cell–cell fusion resulting in the formation of multinucleated cells, is a hallmark of infection by paramyxoviruses and other pathogenic viruses. This natural mechanism has historically been a diagnostic marker for paramyxovirus infection in vivo and is now widely used for the study of virus-induced membrane fusion in vitro. However, the role of syncytium formation in within-host dissemination and pathogenicity of viruses remains poorly understood. The diversity of henipaviruses and their wide host range and tissue tropism make them particularly appropriate models with which to characterize the drivers of syncytium formation and the implications for virus fitness and pathogenicity. Based on the henipavirus literature, we summarized current knowledge on the mechanisms driving syncytium formation, mostly acquired from in vitro studies, and on the in vivo distribution of syncytia. While these data suggest that syncytium formation widely occurs across henipaviruses, hosts, and tissues, we identified important data gaps that undermined our understanding of the role of syncytium formation in virus pathogenesis. Based on these observations, we propose solutions of varying complexity to fill these data gaps, from better practices in data archiving and publication for in vivo studies, to experimental approaches in vitro.

Inactivation Methods for Experimental Nipah Virus Infection

“…During the replication of enveloped viruses, viral attachment and fusion proteins, together with receptors expressed on neighboring cell membranes, can lead to syncytia formation [ 19 ]; this is a hallmark of NiV infection, where syncytia can be observed in vitro but also in vivo in multiple organs such as the lungs, the brain, or the kidneys, amongst others [ 20 ]. Hence, the fusion of neighboring cells can generate multinucleated giant cells during NiV infection that allow the direct cell-to-cell transmission of NiV particles without the necessity for budding, thus accelerating the dissemination of the virus [ 21 ].…”

A potent Henipavirus cross-neutralizing antibody reveals a dynamic fusion-triggering pattern of the G-tetramer

“…HNV entry involves host receptor-induced spatiotemporally sequential conformational cascades of G and F 52 . A recent study provided a new understanding of how the G stalk affects G/F interactions and membrane fusion 53 .…”

Multifaceted activation of STING axis upon Nipah and Measles virus-induced syncytia formation

“…In addition, MeV H from vaccinal strains also interacts with the ubiquitously expressed CD46 receptor 31,32 . The expression of G/H and fusion (F) envelope glycoproteins on the surface of infected cells during viral replication induces cell-to-cell fusion, leading to the formation of multinucleated giant cells named syncytia both in vitro and in vivo 33,34 .…”