Grazing protists foster zebrafish virus transmission

Abstract

Virus transmission is facilitated by diverse means, ranging from particles hitchhiking on dust and other fomites to vector-borne replication. Aquatic ecosystems are rich with interactions between species at various trophic levels, but how these interactions influence virus transmission and infection biology is largely unknown. By mixing zebrafish picornavirus 1 (ZfPV-1) with a panel of freshwater microbial eukaryotes, we found that phagocytic cells promote virus infections in larval zebrafish, even though the virus is unable to replicate in these microbes. Ciliates, which act as crucial concentrators of micronutrients via continuous grazing behavior, stood out as promoters of robust and accelerated virus infections. We found that simply adding the model ciliate Tetrahymena thermophila to mixed populations of infected and uninfected zebrafish facilitated chains of experimental ZfPV-1 transmission between fish. This process depends on Tetrahymena phagocytosis and is likely due to the ability of the ciliates to deliver a concentrated bolus of viruses when consumed by larval fish. Notably, the pathogenic snakehead rhabdovirus was not transmitted after mixing with Tetrahymena, revealing selectivity, potentially through coevolution with ZfPV-1, that is not evident in all RNA fish viruses. We propose that non-host ciliates can act as virus vessels that increase virus transmission between hosts while potentially altering courses of infection by boosting zebrafish immunity. Virus vessels fill a crucial space on the continuum of virus transmission dynamics for viruses lacking the ability to replicate in intermediate species. Given the tools available to manipulate these genetically accessible systems, this paradigm opens new avenues for investigating otherwise hidden features of infection biology with experiments better approximating natural complexity in the wild.