How technology advances are helping scientists tackle zoonotic diseases

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In 2024, the World Health Organization added 24 pathogens to its pandemic watchlist, including three that are zoonotic, meaning they spread from animals to humans. The newly added zoonotic diseases include avian influenza, mpox (previously known as monkeypox) and Sin Nombre virus, the latter of which jumps from mice to people and has a 30% fatality rate in people. In fact, an estimated 60% of infectious diseases that pose a serious threat to people come from animals.

The rise in zoonotic diseases has prompted a call for more comprehensive research into these pathogens. Improving the understanding of zoonotic diseases will help public health officials identify sources of infection, so they can formulate rapid responses to contain human-to-human transmission and develop vaccines. Accelerating research into these diseases will be crucial for preventing global public health emergencies.

At the center of zoonotic disease research is next-generation genetic testing of samples from infected animals and people. In addition to performing whole-genome sequencing, the evolutionary biologists studying zoonosis rely on RNA sequencing, proteomics, immunomics and other advanced techniques, all of which are becoming more efficient with increased automation. These technologies allow evolutionary biologists to study how viruses behave over time, so they can model anticipated transmission and spread. The insights derived from the research could also facilitate rapid vaccine development.

What sparks a pandemic?

In understanding the work of evolutionary biologists and the technology they use to study zoonotic diseases, it’s helpful to consider wildfires as a metaphor for zoonosis. The spark is the animal shedding the virus. For that spark to become a wildfire — a human pandemic — the virus must clear two big bottlenecks: It has to jump from the animal to a human, and then it has to be transmitted from person to person. To figure out how a zoonotic virus clears those bottlenecks, evolutionary biologists must study viruses in both humans and animals.

The technologies used to probe zoonotic viruses are central to advancing the understanding of why some viruses travel from animals to people, and importantly, why they behave differently after they make that jump. Take COVID-19, for example. In the early days of the pandemic, it became clear that some of the deaths from the disease were caused by inflammation in the body emanating from the immune response. This response is dampened in bats, which are carriers of COVID-19 and other coronaviruses but are often asymptomatic.

Researchers are delving into the differences between animal and human immune responses to coronaviruses. One team, for example, discovered three genetic mutations in bats that suppress the ability of the virus to activate the inflammasome, the complex of proteins that promote inflammation. Other research groups have developed single-cell transcriptomic maps of bats’ immune systems, in the hopes of better understanding their molecular responses to viruses and potentially translating the findings to the development of human therapies. One such study revealed that in bats, the increased expression of genes involved in T cell activation contributed to their ability to resist viral infections. Increased profiling of T cells and other immune cells, including natural killer (NK) cells, in both animals and humans will allow researchers to draw correlations and ultimately gain a better understanding how some animals can carry and transmit viruses but not become sick from them.

Embracing automation

One of the major advances in genomics over the last decade has been “long-read” sequencing. This technique allows researchers to sequence DNA fragments that are up to 1,000 of kilobases in length or even longer. This technology has greatly enhanced researchers’ ability to study genomes in the context of immune responses to pathogens. It facilitates RNA sequencing and the probing of complex DNA regions. Long-read sequencing helps researchers detect RNA modifications in viruses that would not be visible using other methods, and it improves research into complex viral transcriptomes, in turn increasing the understanding of gene expression in poorly understood viruses.

Automation is helping to improve long-read sequencing by optimizing extraction and preparation of DNA samples. One key consideration in this process is the need to shear DNA fragments for library construction. Manual processes are slow and error-prone: Using a column-based system to prepare 96 samples can take 100 minutes and over 600 pipette procedures. With automation, by contrast, preparing 96 samples takes just 40 minutes and requires fewer than 200 pipette actions.

Zoonotic research is being boosted by several other up-and-coming technologies. They include “Hi-C,” a high-throughput method for studying the three-dimensional structure of chromatin in cells. This helps researchers determine immune cell subtypes activated by viral infections, and how chemicals called chemokines and cytokines that are released from the body touch off both innate and adaptive immune responses. Another technology, VirScan, offers a high-throughput method for scanning the blood of animals and people to detect both active and resolved viral infections. Using just one drop of blood, researchers can use the technology to find antibodies produced by more than 1,000 strains of viruses, providing another method for studying the interactions between viruses and the immune system.

Advances in zoonosis research

Researchers around the world are demonstrating the benefits that automation is bringing to the study of zoonotic diseases. In January, for example, a team from the University of Montreal described an automated immunofluorescence (IFA) assay for detecting porcine circovirus type 2 (PCV2), which has not been transmitted to people but is considered a zoonotic threat because it has been shown to infect human cells. The researchers are studying PCV2 in swine trachea cells, measuring viral proteins, antigens, mRNA expression and other processes that could shed light on the ability of the virus to infect humans. Previously, producing antigen-coated 96-well microplates for PCV2 assays took a week. That process is now fully automated, as is dilution, microplate washing and image acquisition and analysis, allowing the lab to run eight 96-well microplates in less than six hours, the researchers reported at the Plant and Animal Genome Conference in San Diego.

The mpox outbreak of 2022 has inspired a range of single-cell studies aimed at improving the understanding of how the virus behaves in people — and here, too, automation has been critical. Single-cell RNA sequencing is allowing researchers to measure the impact of the virus on different types of immune cells, which is helping shed light on the impact of the virus in different patient groups. Noting that mpox is more prevalent in patients with HIV, one research team in China used single-cell RNA sequencing to analyze the immune response to the virus in both HIV-positive and HIV-negative patients. They discovered dysregulation of gene expression in the B cells of HIV-positive patients, as well as decreased subsets of natural killer cells and expansion of some CD8 T cells. Such insights into viruses are vital for the development of diagnostics, therapies, and public health interventions, the authors argued in a recent study.

The more artificial intelligence is embedded into next-generation sequencing tools, the better they will become at analyzing zoonosis. Using information about the three-dimensional structure of viral proteins in animals, researchers can use Artificial Intelligence (AI) to predict the ability of those proteins to bind to human receptors. If they identify mutations that enable such binding, they can feed that information into the AI algorithms. It’s easy to see how this technology will become more and more useful for analyzing, and ultimately containing zoonosis.

New technology is also improving vaccine discovery and design. Transcriptome analysis, enabled by automation, can rapidly identify promising vaccine targets. Experimental vaccines can be tested in cellular models such as organoids, allowing researchers to observe which parts of the immune system are getting activated and the effect of candidate vaccines on improving the ability of immune cells to destroy infected cells. Automation streamlines these workflows, improving efficiency while also ensuring consistent, reliable data.

These technologies will become increasingly important as public health officials continue to prioritize pathogen genomic surveillance. Last November, the WHO announced $2 million in grants to support the ability of low- and middle-income countries to build pathogen genomic surveillance capacities. As these and many other projects move forward, advanced sequencing technologies will continue to play a key role in helping researchers identify sources of infection and improving the ability of public health authorities to understand, contain and respond to zoonotic outbreaks.

Partha Banerjee is Senior Manager of Applications at Beckman Coulter Life Sciences, where he leads workflow development and marketing for the Automation and Genomics portfolio focusing on genomics, next-generation sequencing, biologics, drug discovery and proteomics. He has previously worked as a staff research scientist at the Indiana Biosciences Research Institute and The Johns Hopkins University School of Medicine. He has worked in the fields of immunology and cardiology studying protein post-translational modifications (PTMs). Partha has a PhD in Biochemistry from SUNY Stony Brook, NY, where he developed novel viral vectors for gene therapy applications.

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