Viral discovery gone mainstream

There are more viruses in the ocean than there are estimated stars in the universe (~10³⁰), and they will shine like Christmas morning. By necessity, aquatic viral studies have innovated tools that now are fundamentally important in understanding viral epidemics, both in humans and economically and ecologically valuable wildlife species.

Our lab studies viruses in the wild, including those associated with unexplored creatures such as corals, marine mammals, crustaceans, fish and seaweeds. Normally our genomics-based exploration is niche, but last year everything changed. Everywhere we went we heard discussions of how our field of viral discovery was becoming mainstream. Simultaneously, like many scientists, our work came to a standstill. Access to our own lab was reduced. Materials and reagents – including filters and fluorescent dyes – evaporated. Pipette tips, gloves and nucleic acid extraction kits all became limited, and in some cases, extremely expensive commodities. While we typically waited days to receive genomic data, we were instead delayed by weeks to months. Instead, these resources were diverted to the critical endeavour of studying one virus: SARS-CoV-2. This single virus has altered humanity’s knowledge about the world of viruses and forever (hopefully) adjusted our understanding of the importance of studying unknown viral diversity and mechanisms of wildlife viral infection and transmission.

The current viral pandemic reminds us that we are humans living in a microbial world. Viruses are indispensable to our evolution and continued survival. Viruses safeguard biodiversity, facilitate biogeochemical cycling, initiate carbon sequestration and are a repository for genetic innovation in nearly every ecosystem. They are likely the reason we have evolved to be born with a placenta and can inadvertently help us prevent or fight bacterial infections. Yet viruses, as this single year as tragically shown, can sometimes be one of humanity’s biggest calamities, leading to millions of our deaths and/or disabilities in a very short period of time. The emergence and spread of SARS-CoV-2 is an explicit reminder that we exist in lockstep with these obligate genetic parasites. The advanced viral research methods and the rapidity of vaccine development demonstrate that our technologies have enabled us to remain somewhat in the race to identify and ideally mitigate emergent human epidemics.

SARS-CoV-2 also aptly illustrates that viral infections are hardly unique to humans – wildlife also engages in a constant evolutionary battle with viruses. The epidemiological dynamics of the SARS-CoV-2 pandemic are analogous to many emerging infectious diseases (EIDs) in all ecosystems. EIDs in the marine realm have inflicted billions of US dollars in losses in the aquaculture industry and cause significant risks to aquatic community stability, biodiversity and conservation efforts. The inception of these EIDs often follow two patterns: (a) a change in host distribution; or (b) a change in microbial (pathogen) phenotype. Increasingly, both may be driven by habitat encroachment and/or destruction. For example, changes in land use can lead to altered migration routes, forced proximity of species or increases in host density. Likewise, trade and host stress (e.g., eutrophication, hypoxia, climate change etc.) can alter animal distribution and ecology. Any combination of these factors can modify microbial transmissibility, pathogenicity or persistence. The consequences of EIDs within marine ecosystems has resulted in what virologists call mass mortality events (MMEs), which have been escalating incrementally. Open to debate is whether MMEs are due to greater detection efforts or external factors. With clear parallels between emerging wildlife disease and potential zoonoses, it is apparent that exploring viral diversity in our environment is paramount, as this form of basic research may identify spillover events that can escalate into pandemics such as COVID-19.

Over several decades, a community of microbiologists and virologists has developed a repertoire of tools and databases to sequence, identify and visualise viruses, allowing more scientists to explore which viruses are in that backyard pond. We no longer need to isolate and cultivate the viruses we wish to study, resulting in an ever-growing viral taxonomic inventory. These tools mean that we can identify and characterise currently unculturable viruses by detecting their genomic information in a variety of hosts and habitats: guts, animal tissue, plants, fungi, clinical specimens and just about anything really. The massive amount of data we can produce to sequence viral genomes, combined with projections that Moore’s law of computing power will soon become obsolete, usher in a never-before-seen opportunity to discover and understand the ecology and evolution of viruses.

The technologies we now use for viral discovery are fundamentally ‘democratising’ the field. Many of these tools, ranging from phi polymerase to viromic sequencing itself, were developed out of need from researchers working on environmental systems, yet have been critically important for the interrogation of SARS-CoV-2 during this pandemic. The availability and approachability of both ‘hardware’ (e.g., field, bench, sequencing tools) and ‘software’ (e.g., bioinformatic tools) opens the gates to those invested in both the exploration of human pathogens and viruses in underexplored hosts alike. For example, in the early 1980s, during the beginning of the AIDS epidemic, it took ~2 years to isolate, visualise and confirm the association of HIV with the syndrome using culturing, immunology, cytology and microscopy research methods. Some 20 years later, during the 2003 SARS outbreak, it took 4 months to identify the culprit as coronavirus primarily through orthologous gene sequence and RT-PCR. Yet, although the SARS-CoV-2 epidemic began in December 2019, the viral phylogeny and complete ribonucleic acid genome were published within 1 month due to the remarkable advancements in high-throughput sequencing, genome assembly methods and viral genome database enrichment, largely using tools originally developed outside of a clinical setting.

Although SARS-CoV-2 has immobilised our world and caused incalculable harm, this pandemic has already changed the way science, research and medicine are conducted. The effects of the pandemic on future viral research are profound. Furthermore, the SARS-CoV-2 outbreak makes it clear to the broader public, many human disease experts and clinicians that the human and societal cost of zoonoses is no longer hypothetical. Recent years have brought a groundswell of methods to investigate the larger epizootic pool to preserve both ourselves and global biodiversity. These tools highlight the utility of viral discovery for the sake of discovery and ideally the prevention, isolation and/or mitigation of future outbreaks. However, they also indicate the essential nature of democratised in silico tools and increasing databases of sequenced genomes and microscopic discovery. This genomic era is simply the beginning of a new era of research in ‘environmental viromics.’ The ever-enigmatic viral sequences we detect in silico are not always able to give us full insights into their importance or roles in host health and disease. Therefore, while the first steps to detect viruses in the wild are becoming more efficient, developing a true understanding of how these viruses work (infect, replicate, integrate) is a complex task. While the pandemic may have temporarily evaporated some of the physical resources from the environmental virology community, it replaced them with another invaluable one – human capital. In the face of the next epizootic or epidemic, humanity will have a new and educated cohort – conscious of their context in a viral world and motivated to discover the infinity of viruses around them, including those in their backyard.