Virus Discovery in the 21st Century

Abstract

Abstract Viral discovery poses challenges distinct from those associated with other microbial agents, such as bacteria, fungi and parasites. With the exception of mimiviruses and megaviruses, where imaging is feasible by optical microscopy, viruses cannot be detected without resorting to specialized electron microscopy. Furthermore, viruses lack correlates of the conserved bacterial 16S ribosomal ribonucleic acid (rRNA) gene sequences and fungi's 18S rRNA or internal transcribed spacer gene sequences that facilitate detection and phylogenetic characterisation through polymerase chain reaction (PCR) amplification. Virus discovery during most of the twentieth century followed a classical approach comprising isolation in cell culture or animal models, followed by morphological classification by electron microscopy and studies of serological properties. In the late twentieth century, advances in nucleic acid sequencing have revolutionised virus discovery by enabling cultivation‐independent methods for virus detection and classification. Here, we review current methods for virus discovery and characterisation and provide our perspective on likely future advances in this field. Key Concepts: Recent advances in nucleic acid sequencing enable cultivation‐independent methods for microbial diagnosis surveillance and discovery. Viruses are ubiquitous and play important roles in global ecology and evolution as well as in disease. Classical methods such as culture and serology remain important despite the increasing emphasis on molecular assays in microbiology. Zoonoses, infections that jump from domestic animals and wildlife to humans, account for the majority of emerging infectious diseases. Microbial discovery must be linked to rigorous validation strategies to reduce risks for errors that can profoundly impact public health.