Phosphatidylserine Vesicles Enable Efficient En Bloc Transmission of Enteroviruses

A central paradigm within virology is that each viral particle largely behaves as an independent infectious unit. Here, we demonstrate that clusters of enteroviral particles are packaged within phosphatidylserine (PS) lipid-enriched vesicles that are non-lytically released from cells and provide greater infection efficiency than free single viral particles. We show that vesicular PS lipids are co-factors to the relevant enterovirus receptors in mediating subsequent infectivity and transmission, in particular to primary human macrophages. We demonstrate that clustered packaging of viral particles within vesicles enables multiple viral RNA genomes to be collectively transferred into single cells. This study reveals a novel mode of viral transmission, where enteroviral genomes are transmitted from cell-to-cell en bloc in membrane-bound PS vesicles instead of as single independent genomes. This has implications for facilitating genetic cooperativity among viral quasispecies as well as enhancing viral replication. [Display omitted] •Clusters of viruses are packaged and released non-lytically in PS lipid vesicles•PS lipids are co-factors in mediating subsequent infectivity and transmission•PS vesicles provide greater infection efficiency for viruses•PS vesicles enable viral genome clusters to be transmitted en bloc cell-to-cell Clusters of enteroviruses are packaged in phosphatidylserine (PS)-enriched vesicles, thereby enhancing the infection efficiency of the viruses and enabling collective transmission of multiple viral genomes from cell-to-cell.