Viral Evolution in Animals Could Reveal Future of COVID-19

When animals get COVID-19 from humans, new SARS-CoV-2 variants can develop. To evaluate this phenomenon, an interdisciplinary team from the College of Veterinary Medicine and Biomedical Sciences systematically analyzed mutation types that occur in the virus after infection of cats, dogs, ferrets and hamsters.

Confirmed cases of COVID-19 in a variety of wild, zoo and domestic animals demonstrate interspecies transmission, which is rare for most viruses.

“SARS-CoV-2, in the field of coronaviruses, has a very broad species range,” said Laura Bashor, one of the first authors and a doctoral student in the Department of Microbiology, Immunology and Pathology. “In general, many types of viruses cannot infect other animal species. They have evolved to be very specific.”

“People are exposed to many different animals so often that this virus had the opportunity to expose a variety of different species,” said Erick Gagne, a first author and now an assistant professor of ecology of natural diseases at the University of Pennsylvania. .

The global reach and spread of the virus has given researchers a unique opportunity to investigate the viral evolution of SARS-CoV-2, including in the lab of University Distinguished Professor Sue VandeWoude at Colorado State University.

These feline and domestic cat disease transmission specialists applied their experience in sequence analysis and genomes study to SARS-CoV-2. The study was recently published in PNAS, the official journal of the National Academy of Sciences.

Emerging Mutations

Researchers in the VandeWoude lab teamed up with assistant professor Angela Bosco-Lauth and Professor Dick Bowen of the Department of Biomedical Sciences, who used their animal modeling expertise to develop a test for SARS-CoV-2 susceptibility of animal species.

Also key to the findings was a newer sequencing technique of the virus at different stages of research, now common to detect variants in the human population. Mark Stenglein, an associate professor in the Department of Microbiology, Immunology and Pathology, provided computational skills in analyzing biological molecular sequences, also known as bioinformatics, for the study.

“We found that there was evolution, we saw selection for the virus, and we saw many variants emerge in the genome sequence of the virus,” Bashor said.

To provide enough viral material for the study, Bosco-Lauth and Bowen cultured a human SARS-CoV-2 sample in cells grown in the lab. Bashor and Gagne found that at each step of this process, multiple mutations developed and became a larger percentage of the genetic population.

The virus was then introduced to the four household species and samples of the virus were collected from their nasal passages after infection.

PhD candidate Laura Bashor works in the VandeWoude Lab at Colorado State University. Credit: Colorado State University

“In the animals, the cell culture variants reverted to the original human type, indicating that adaptation is likely taking place in that cell culture and environment selected for those variants,” Gagne said.

Not all of these mutations within the cell culture SARS-CoV-2 variant were transferred into the new hosts. Instead, several mutations emerged in the virus secreted by the living animals.

The first viral sample in the study was isolated in early 2020. The team observed mutations that have since formed widespread SARS-CoV-2 strains in the human population at an accelerated rate throughout the study.

“Among them were some that we’ve seen in humans since then in the alpha, beta, delta variants,” says Dr. Sue VandeWoude, senior author. “There were specific genetic code changes that mimicked what other scientists have reported in humans.”

Contact exposure between two cats showed that the SARS-CoV-2 variant can be transmitted with the ability to produce a new strain within the species.

“We see that in people too,” says Bosco-Lauth. “Hosts that are really well adapted to support SARS-CoV-2 infection are also very good at allowing these mutations to linger and be passed on.”

The future

Bashor did not anticipate studying SARS-CoV-2 when she came to CSU during the pandemic to begin her doctoral studies. However, it presented a unique opportunity as a graduate student to embark on a “really cool and viable project” in the ecology and evolution of disease.

Gagne completed his postdoctoral research on the transmission of feline retroviruses between species in the VandeWoude lab when the team launched the SARS-CoV-2 study. Now an assistant professor, he has continued to investigate SARS-CoV-2 spillover with the Wildlife Futures program at the University of Pennsylvania.

Graduate students and early scientists such as Bashor and Gagne have made meaningful contributions to SARS-CoV-2 research, VandeWoude said.

The team continued their research to focus on cats, as they have shown a greater susceptibility to COVID-19 spillover from humans and can produce variants of the virus and spread to other cats.

Bashor began by analyzing SARS-CoV-2 genome sequences from a large pool of cat species around the world, including tigers, lions and snow leopards. The publicly available data from infected cats may provide additional insights into the adaptability and variability of COVID-19 within and between feline species.

There is no evidence of transmission from cats to humans. But cats remain susceptible to all variants of COVID-19 in the human population.

By understanding viral evolution in cats, the research team can find answers to the question: What is the future of SARS-CoV-2 for humans and animals?

Reference: “SARS-CoV-2 evolution in animals suggests mechanisms for rapid variant selection” by Laura Bashor, Roderick B. Gagne, Angela M. Bosco-Lauth, Richard A. Bowen, Mark Stenglein, and Sue VandeWoude, October 29, 2021, Proceedings of the National Academy of Sciences.
DOI: 10.1073/pnas.2105253118

Funding: Colorado State University College of Veterinary Medicine and Biomedical Sciences Research Council Award, NIH/National Center for Advancing Translational Science Colorado Clinical and Translational Science Awards