PT - JOURNAL ARTICLE AU - Fabio Zanini AU - Szu-Yuan Pu AU - Elena Bekerman AU - Shirit Einav AU - Stephen R. Quake TI - Single-cell transcriptional dynamics of flavivirus infection AID - 10.1101/203331 DP - 2018 Jan 01 TA - bioRxiv PG - 203331 4099 - http://biorxiv.org/content/early/2018/01/18/203331.short 4100 - http://biorxiv.org/content/early/2018/01/18/203331.full AB - Dengue and Zika viral infections affect millions of people annually and can be complicated by hemorrhage or neurological manifestations, respectively. However, a thorough understanding of the host response to these viruses is lacking, partly because conventional approaches ignore heterogeneity in virus abundance across cells. We present viscRNA-Seq (virus-inclusive single cell RNA-Seq), an approach to probe the host transcriptome together with intracellular viral RNA at the single cell level. We applied viscRNA-Seq to monitor dengue and Zika virus infection in cultured cells and discovered extreme heterogeneity in virus abundance. We exploited this variation to identify host factors that show complex dynamics and a high degree of specificity for either virus, including proteins involved in the endoplasmic reticulum translocon, signal peptide processing, and membrane trafficking. We validated the viscRNA-Seq hits and discovered novel proviral and antiviral factors. viscRNA-Seq is a powerful approach to assess the genome-wide virus-host dynamics at single cell level.