Visualizing active viral infection reveals diverse cell fates in synchronized algal bloom demise

Marine viruses are considered as major evolutionary and biogeochemical drivers of microbial life, through metabolic reprogramming of their host and cell lysis that modulates nutrient cycling1, primary production and carbon export in the oceans2. Despite the fact that viruses are the most abundant biological entities in the marine environment, we still lack mechanistic and quantitative approaches to assess their impact on the marine food webs. Here, we provide the first quantification of active viral infection, during bloom succession of the cosmopolitan coccolithophore Emiliania huxleyi, by subcellular visualization of both virus and host transcripts on a single cell resolution across thousands of cells. Using this novel method, that we coined Virocell-FISH, we revealed that distinct transcriptional states co-exist during the infection dynamics, and that viral infection reached only a quarter of the E. huxleyi population although the bloom demised in a synchronized manner. Through a detailed laboratory time-course infection of E. huxleyi by its lytic large virus EhV, we quantitatively show that metabolically active infected cells chronically release viral particles, and that viral-induced lysis is not systematically accompanied by virion increase, thus challenging major assumptions regarding the life cycle of giant lytic viruses. Using Virocell-FISH, we could further assess in a new resolution, the level of viral infection in cell aggregates, a key ecosystem process that can facilitate carbon export to the deep ocean3. We project that our approach can be applied to diverse marine microbial systems, opening a mechanistic dimension to the study of host-pathogen interactions in the ocean. One Sentence SummaryQuantifying active viral infection in algal blooms