SARS-CoV-2 develops after jumping from humans to zoo animals

SARS-CoV-2 develops after jumping from humans to zoo animals

A detailed genomic study of an outbreak at the Denver Zoo shows how SARS-CoV-2 can rapidly diversify and adapt after crossing species, offering a rare real-world glimpse into virus evolution beyond humans.

Study: Spread, diversification and adaptation of the SARS-CoV-2 population within the host in zoo tigers, lions and hyenas. Image credit: Wirestock Creators/Shutterstock.com

A new study published inNature communicationshows the rapid development and adaptation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in zoo tigers, lions and hyenas that are in daily contact with humans.

How animal infections influence the development and risk of SARS-CoV-2

The rapid development of SARS-CoV-2 and the emergence of new variants have significantly shaped public awareness of infectious diseases since the beginning of the 2019 coronavirus pandemic (COVID-19).

In addition to humans, SARS-CoV-2 infects a variety of domestic and wild animals, and documented cases show that in rare cases the virus can be transmitted from an animal host back to humans. However, the factors driving the evolution and transmission dynamics of SARS-CoV-2 in animals, as well as the origins of new virus variants that infect both humans and animals, are largely unknown.

The selection of beneficial mutations that increase viral fitness is the crucial factor for viral evolution within the host species. Virus populations may face unique and powerful selection pressures following transmission from one host species to another. These spillover events can accelerate the emergence of viral variants by selecting genetic mutations that improve the fitness of the virus in the new host.

To study the effects of host switching on virus evolution, researchers from Colorado State University and their collaborators at the Denver Zoo Conservation Alliance, USA, studied the evolution and host-specific adaptation of SARS-CoV-2 in tigers, African lions and spotted hyenas during an outbreak at the Denver Zoo in 2021.

Genomic tracking reveals rapid adaptation after zoo spillover

The researchers collected nasal swab samples from two tigers, 11 lions and three hyenas, isolated viral RNA from the samples, and performed next generation sequencing (NGS) to identify the SARS-CoV-2 lineage, intra-host variation, and genomic selection signatures.

Results indicated that the Denver Zoo outbreak was likely triggered by a single spillover of a rare delta sublineage, most consistent with transmission from humans (keepers) to tigers and then further to lions and hyenas.

Rapid spread and diversification of virus populations has been observed across animal hosts. The researchers also discovered genomic signatures of both negative selection (removal of harmful mutations) and positive selection (selection of beneficial mutations) throughout the virus genome, as well as four possible species-specific adaptive mutations in lions and hyenas.

Although no SARS-CoV-2 variants of concern have been detected in infected animals, uniquely strong signatures of positive selection have been detected in the nucleocapsid gene and samples from hyenas, illustrating the combined effects of mutation and selection following cross-species viral transmission.

The study discovered four species-specific mutations, including A254V in the nucleocapsid gene in lions and hyenas, as well as E1724D in the open reading frame 1-alpha, T274I in the spike protein gene and P326L in the nucleocapsid gene in hyenas. These mutations have been rarely detected in humans and are not associated with a specific variant lineage.

Specifically, the study found that while the Denver Zoo outbreak occurred during one of the peaks of the COVID-19 pandemic, the rare Delta lineage that caused the outbreak was linked to less than 1% of human infections in Colorado at the time.

The rarity of this lineage in humans also supports the idea that the zoo outbreak was triggered by a single spillover event, most likely from an infected human. However, the possibility of multiple independent transmission from humans to animals or virus transmission between peridomestic animals in the zoo remains.

The study found the strongest genomic signatures of positive selection in the SARS-CoV-2 nucleocapsid gene, which encodes the RNA-binding nucleocapsid protein responsible for packaging the viral genome.

Mutations in this gene have already been discovered in worrisome SARS-CoV-2 variants that infect people. These mutations have been associated with improved viral replication fitness in experimental and epidemiological studies, suggesting that changes in this gene may influence virus survival and transmissibility in the host environment.

Another notable mutation discovered in the study was the hyena-specific T274I mutation in the spike gene. The mutation could represent an adaptation to the hyena-specific viral entry receptor. Structural and immunological analyzes from human studies suggest that substitutions at this site may also contribute to immune escape. However, the functional consequence of this mutation in hyenas remains to be determined.

The virus populations discovered in the study showed rapid expansion and diversification over time. It is known in the literature that the strength of selection increases as a virus population spreads.

The zoo outbreak offers real insights into virus evolution

Overall, the virus populations isolated from the infected animals showed an approximately equal distribution of both positive and negative selection signatures, with the exception of those isolated from hyenas, which showed uniquely strong positive selection.

The researchers said this difference may be related to the timing of sampling, as hyena samples were collected later in the outbreak and therefore may have been collected later in the course of the infection compared to samples from lions and tigers. These results highlight the possibility of an increased SARS-CoV-2 evolutionary rate in hyenas.

Overall, the study results provide valuable insight into the mechanisms underlying virus evolution within the host following interspecies transmission.

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