Virus particles protect genomes from hostile environments within and outside the host, eventually delivering these genomes to target tissues to initiate infection. Complex processes requiring significant energy and time are necessary to assemble these virus particles, but only a small portion of released virus will successfully infect new target cells (Fig 1A). While the science of virology has developed based on the isolation and purification of viral particles, it is becoming increasingly clear that direct cell-to-cell transmission of viruses and/or viral components is also highly relevant [1, 2].

Direct cell-to-cell spread of infections has several advantages. The first is efficiency: genomic cargo is delivered directly to cells rather than being randomly released into the environment. The second is speed: appropriation of cellular protein trafficking infrastructure allows faster spread within tissues. The third is barrier avoidance: intrinsic immunity and other barriers interfering with entry or post-entry steps in target cells can be bypassed. The fourth is humoral immunity evasion: limited exposure time to the extracellular space allows evasion of neutralizing antibodies.