Fruits of Virus Discovery: New Pathogens and New Experimental Models

The advent of high-throughput sequencing has led to a tremendous increase in the rate of discovery of viral sequences. In some instances, novel pathogens have been identified. What has been less well appreciated is that novel virus discoveries in distinct hosts have led to the establishment of unique experimental systems to define host-virus interactions. These new systems have opened new frontiers in the study of fundamental virology and infectious disease. NEXT-GENERATION SEQUENCING (NGS) CATALYZES THE RATE OF VIRUS DISCOVERY In the past decade, new developments in sequencing technology,along with commensurate bioinformatic capability and tools and their application to interrogate samples for the presence of virus-derived nucleic acids, have led to a dramatic increase in the rate at which novel virus sequences have been discovered. In single studies of diverse specimen types, evidence for literally tens to hundreds of novel viruses can now be generated. This has resulted in a near-quadrupling of the number of unique virus species in GenBank since 2005 (Fig. 1). These observations have demon-strated that the world of viruses is vastly greater than previously recognized. For the past half-century, the predominant viruses that were known and studied were those that could be grown in cell culture systems, and it was only on rare occasions that viruses were identified that could not be cultured (e.g., human norovirus or hepatitis C). Thus, our perspective on the diversity of viruses has been heavily biased toward those that could be propagated in a very limited set of experimental culture systems. In many re-gards, this situation parallels the 1990-era observations in the bac-terial world when consensus 16S rRNA gene sequencing demon-strated a much greater diversity of bacterial taxa than had been previously identified by culturing. The goal of this Gem is to describe the most substantive fruits arising from theNGS revolution. Technical aspects of viral discov-ery by NGS are not discussed here. Rather, the focus is on provid-ing exemplars of novel pathogens and novel model systems that have emerged from the first decade of NGS-based virus-discovery efforts