Exploring virus transmission: How mammal research is shaping disease preparedness

In a world increasingly aware of the impact of emerging diseases, researchers are working to bridge critical gaps in our understanding of how viruses move between species. Nate Upham, an evolutionary biologist and mammalogist, is among those asking questions about the hidden world of mammal-virus interactions. His work focuses on using what we know about wild mammals to improve our understanding of which viruses are shared among hosts.  These ‘known’ mammal-virus interactions can then be used to predict ‘unknown’ interactions, including potential spillover events to humans. His lab was recently awarded an early-stage investigator grant from the National Institutes of Health to conduct this work over the next five years both globally and locally among wild rodents living in Arizona’s Sonoran Desert. Key collaborators include associate professor Beckett Sterner and professor Arvind Varsani in ASU’s School of Life Sciences.

Upham’s academic journey began with studying desert rodents in Nevada before expanding to the fossil record, evolutionary biology and disease ecology. His postdoctoral research eventually led him to analyze the genetics of over 6,000 mammal species globally, mapping their evolutionary history. This foundation in mammal taxonomy became particularly significant in the context of studying viral sharing across species.

"Taxonomy is the science of naming and defining the limits of species. It turns out, what lens different scientists take on defining species can influence the conclusions of different spillover risk analyses," he explained. “We want to bring those assumptions about mammal species to the surface and ask how they influence things like viral sharing models.”

A key aspect of his research is updating and maintaining records of which viruses have been observed with which mammal hosts. "We're trying to keep the mammal-virus interaction data in sync with the latest taxonomy, the latest names and concepts of hosts and viruses," Upham said. This ensures that virologists and epidemiologists have accurate information when analyzing how viruses move through animal populations.

The need for more accurate data became apparent during the COVID-19 pandemic. "The mammal-virus interaction data that scientists were using to make models were really outdated at that time," Upham noted. By better connecting the existing data to evidence from the literature – including how and where viruses were detected and with what degree of confidence – Upham’s team aims to improve models of host-virus ecology.

Beyond large-scale global studies, Upham’s team also conducts fieldwork in Arizona. "We've been developing these field programs on desert rodents, circling back to where I started as an undergraduate and master’s student," he shared. His team collects data on rodents living in isolated forested mountain areas known as the Madrean Sky Islands, analyzing how viruses are shared relative to the shared ancestry of rodent populations.

Their work extends to cities too. "We're doing some similar work across urban desert remnants in the Phoenix metro area," Upham said. These studies help researchers understand how movement barriers affect animal interactions and pathogen exchange in the city.

Fieldwork involves setting traps for nocturnal rodents, collecting tissue samples both lethally and non-lethally, and preserving specimens for the ASU Natural History Collection. "We end up with several hundred tissue samples that are flash-frozen on liquid nitrogen that we bring back to the lab and organize," he said. This research helps build a genomic database to analyze patterns of gene flow and viral sharing among rodent populations.

The partnership with the ASU Natural History Collections is a major enabler of this work, especially collaborations with Dakota Rowsey and Laura Steger. “Collections ensure the long-term preservation of the tissue samples and whole organisms that we collect,” Upham said. “Enabling future researchers to ask questions we haven’t yet thought of is both thrilling and a great reason to keep building this resource.” His lab has benefited by using collections from the 1950s and ‘60s housed at the University of Arizona and ASU, often from populations that are now considerably altered by fire or urbanization.

Studying viruses at a molecular level provides insights into how they evolve with their mammalian hosts. "There are many co-evolutionary relationships between these rodents and viruses that have mutually shaped each other over time," Upham explained. By tracking gene flow, his team hopes to better understand which viruses are transmitted vertically (from parent to offspring) and which are transmitted horizontally (through environmental exposure or unrelated individuals).

"The ones that are vertically transmitted often have a tight relationship with one host species, but if a novel species gets infected they may suffer negative consequences," he noted.

The team’s research has also expanded into studying Valley Fever, a disease caused by the fungal pathogen Coccidioides, which thrives in Arizona’s desert environment. "There’s emerging evidence that the desert rodents in the Phoenix Valley and other parts of the U.S. may serve as the natural reservoir host," Upham said. His team is collaborating with the ASU Health Observatory and researchers at Northern Arizona University to explore this connection.

The field of wild virus research is vast, and much remains unknown. However, studies like this one are crucial to improving our preparedness for potential future outbreaks. "It’s not supposed to alarm people, but we should be ready by having the best knowledge directly available to more people," Upham stated. Through combining taxonomy, genomics and field research, this work will contribute vitally to the study of viral interactions with the natural world.