Department of Bioengineering, Stanford University, Stanford, United States
Szu-Yuan Pu
Division of Infectious Diseases, Department of Medicine, Stanford University School of Medicine, Stanford, United States; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, United States
Elena Bekerman
Division of Infectious Diseases, Department of Medicine, Stanford University School of Medicine, Stanford, United States; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, United States
Division of Infectious Diseases, Department of Medicine, Stanford University School of Medicine, Stanford, United States; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, United States
Stephen R Quake
Department of Bioengineering, Stanford University, Stanford, United States; Department of Applied Physics, Stanford University, Stanford, United States; Chan Zuckerberg Biohub, San Francisco, United States
Dengue and Zika viral infections affect millions of people annually and can be complicated by hemorrhage and shock 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.
