Direct Intercellular Transport Mode of Filovirus Nucleocapsids

Intercellular pathways of viral infection in host cells offer advantages, such as efficiency of viral spread and immune surveillance evasion, compared to cell-free viral infection. Therefore, some enveloped viruses present both cell-to-cell and cell-free forms of infection in the host organisms. In this study, we investigated the occurrence of Ebola virus (EBOV) and Marburg virus (MARV) nucleocapsid exchange in vitro between interconnected Huh7 cells using live-cell imaging methods. Moreover, through plasmid transfection methods, we demonstrated that nucleocapsid-like structures (NCLSs) formed with EBOV NP, VP35, VP24, and VP30 proteins can also be transported intercellularly to non-transfected cells through cell-to-cell contact regions in a process involving interaction with the host cell actin cytoskeleton. Our results provide further evidence of cell-to-cell transport as a mechanism of filovirus spread and support the need for further research in this field to develop new intervention methods targeting this transmission pathway.