Single-cell RNA-seq methods to interrogate virus-host interactions

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Abstract
The twenty-first century has seen the emergence of many epidemic and pandemic viruses, with the most recent being the SARS-CoV-2-driven COVID-19 pandemic. As obligate intracellular parasites, viruses rely on host cells to replicate and produce progeny, resulting in complex virus and host dynamics during an infection. Single-cell RNA sequencing (scRNA-seq), by enabling broad and simultaneous profiling of both host and virus transcripts, represents a powerful technology to unravel the delicate balance between host and virus. In this review, we summarize technological and methodological advances in scRNA-seq and their applications to antiviral immunity. We highlight key scRNA-seq applications that have enabled the understanding of viral genomic and host response heterogeneity, differential responses of infected versus bystander cells, and intercellular communication networks. We expect further development of scRNA-seq technologies and analytical methods, combined with measurements of additional multi-omic modalities and increased availability of publicly accessible scRNA-seq datasets, to enable a better understanding of viral pathogenesis and enhance the development of antiviral therapeutics strategies.
Funding Information
  • NIH Office of the Director (DP1 DA045089)
  • Bill and Melinda Gates Foundation (OP113682, OP113682)
  • NIH (U19AI109662, T32 AI00729037, T32 GM007364)
  • NIH (F31 AI172311)
  • Bio-X Graduate Fellowship
  • National Science Foundation (2019282939)
  • Department of Defense (W81WXH-18-1-0253, W91XWJ10235)
  • Dr. Ralph and Marian Falk Medical Research Trust
  • Chan Zuckerberg Biohub

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