Dissecting viral infections, one cell at a time, by single-cell technologies

The meteoric rise of single-cell genomic technologies, especially of single-cell RNA-sequencing (scRNA-seq), has revolutionized several fields of cellular biology, especially immunology, oncology, neuroscience and developmental biology. While the field of virology has been relatively slow to adopt these technological advances, many works have shed new light on the fascinating interactions of viruses with their hosts using single cell technologies. One clear example is the multitude of studies dissecting viral infections by single-cell sequencing technologies during the recent COVID-19 pandemic. In this review we will detail the advantages of studying viral infections at a single-cell level, how scRNA-seq technologies can be used to achieve this goal and the associated technical limitations, challenges and solutions. We will highlight recent biological discoveries and breakthroughs in virology enabled by single-cell analyses and will end by discussing possible future directions of the field. Given the rate of publications in this exciting new frontier of virology, we have likely missed some important works and we apologize in advance to the researchers whose work we have failed to cite.