Virus Discovery in the 21st Century

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.

New Parvovirus Associated with Serum Hepatitis in Horses after Inoculation of Common Biological Product

“…We used an unbiased amplification and high-throughput sequencing approach to identify known and new viruses in the antitoxin and liver sample ( 19 , 23 , 30 ). Bioinformatics of sequence data revealed a 4.5-kb base assembled sequence in the horse liver sample that showed distant yet significant protein similarity with known bovine and porcine parvoviruses.…”

“…We generated a phylogenetic tree showing sequences used for the comparison and their GenBank accession numbers (Figure 1, panel A). The evolutionary history was inferred by using the maximum-likelihood method based on the Le_Gascuel_2008 model ( 23 ). The tree with the highest log likelihood is shown.…”

Virome Analysis of Transfusion Recipients Reveals a Novel Human Virus That Shares Genomic Features with Hepaciviruses and Pegiviruses

“…The unusually high infection prevalence of hepatitis C virus (HCV), HBV, and HIV in hemophilia patients and other transfusion recipients could have been prevented by earlier identification of these viruses and development of accurate diagnostic assays ( 3 – 8 ). Advances in sequencing platforms have revolutionized identification of new viruses ( 9 ) and have been widely adopted for identification and characterization of viruses that infect humans and animals ( 10 – 15 ). Genetic characterization of new viruses is a first crucial step toward their molecular and biological characterization.…”

“…Genetic characterization of new viruses is a first crucial step toward their molecular and biological characterization. Sequence data of a new virus not only help in estimating its biological properties but also enable development of molecular reagents that can be used for molecular diagnostics and epidemiological and clinical investigations of their transmission and disease associations ( 9 ).…”

Phylodynamic applications in 21st century global infectious disease research

“…But what can we do if we have no knowledge regarding a particular organism or population? This has become a more pertinent issue recently with the increasing rate of discovery, facilitated by NGS, of organisms for which we have limited prior knowledge, such as novel viruses and bacteria, [60]. One of the advantages of the Bayesian phylodynamic approach is the ability to test multiple hypotheses regarding the evolution or epidemiological models used to describe infectious disease behavior, but because of the intricate relationship of these models, reliable inferences require testing of all combinations of the individual proposed models.…”