Cell-to-cell heterogeneity drives host-virus coexistence in a bloom-forming alga

Algal blooms drive global biogeochemical cycles of key nutrients in the oceans and serve as hotspots for biological interactions. The massive spring blooms of the cosmopolitan coccolithophore Emiliania huxleyi (E. huxleyi) are often infected by the lytic Emiliania huxleyi specific virus (EhV) which is a major mortality agent triggering bloom demise. Nonetheless, the multi-annual 'boom and bust' pattern of E. huxleyi suggests that mechanisms of coexistence are essential for these host-virus dynamics. To investigate host-virus coexistence, we developed a new model system from an E. huxleyi culture which recovered from viral infection. The recovered population coexists with the virus, as host cells continue to grow in parallel to viral production. By applying a single-molecule fluorescence in situ hybridization (smFISH) approach to quantify the fraction of infected cells and assessing infection-specific lipid biomarkers, we identified a small subpopulation (5-7% of cells) that was infected and produced new virions, whereas the majority of the host population could resist infection. To further assess population heterogeneity, we generated monoclonal strain collections using single-cell sorting and subsequently phenotyped their susceptibility to EhV infection. This unraveled a substantial cell-to-cell heterogeneity across a continuum of susceptibility to resistance, suggesting that infection outcomes may vary depending on the individual cell. These results add a new dimension to our understanding of the complexity of host-virus interactions that are commonly assessed in bulk and described by binary definitions of resistance or susceptibility. We propose that phenotypic heterogeneity drives E. huxleyi-EhV coexistence and may potentially provide the coexisting strain an ecological advantage by killing competing susceptible strains.