Unmasking cellular response of a bloom - forming alga to virus infection by 1 resolving expression profiling at a single - cell level

14 The interaction between Emiliania huxleyi, a bloom-forming alga, and its specific large virus 15 (EhV), is one of the most ecologically important algal-virus model system. Infection by EhV 16 depends on profound rewiring of metabolic network to supply essential building blocks for viral 17 assembly. Despite the clear evidence for the modulation of the host metabolic and signaling 18 pathways during infection, there is a major bottleneck to accurately discern between viral hijacking 19 strategies and host defense responses. Here we uncovered cell-to-cell heterogeneity of isogenic 20 cell population by host and virus gene expression profiling at a single cell level. This approach 21 enabled mapping of cells into newly defined infection states. Clustering of cells based on their 22 infection state and examination of host gene expression profiles unmasked a yet unrecognized 23 early phase in host response that occurs prior to viral expression. This early response includes the 24 induction of genes involved in cell fate regulation, ROS metabolism and sphingolipid catabolism. 25 Upregulation of various host metabolic genes coincided with late-viral gene and their expression 26 was suppressed in stationary phase cells which exhibited compromised infection. We propose that 27 peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission. The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/186981 doi: bioRxiv preprint first posted online Sep. 12, 2017;