There is tremendous enthusiasm for using the power of transcriptomics to unravel the state of single cells in tissues and tumors. If a single-cell profiling method is to be meaningful, however, it must be i) technically reproducible, ii) sensitive to low-abundance molecules, and iii) compatible with cells isolated in situ. There are many exciting techniques under development to profile the transcriptomes of single cells; unfortunately, none of them meet any of these three criteria.

Coxsackievirus B3 (CVB3) is a cardiotropic positive-strand RNA virus that is a leading cause of viral myocarditis and heart failure in infants and young children. Nearly all work on CVB3 virology has focused on the docking interactions and gene products of the virus. Sparked by an early collaboration with the McManus laboratory (University of British Columbia), my group has taken a fundamentally different view of CVB3 pathogenesis as a systems-level perturbation of the host.