Chinese farmed fur animals found to harbor dozens of novel viruses

Hidden reservoirs: Mink, raccoon dogs, and other fur animals may be breeding grounds for the next pandemic, with newly discovered viruses posing a serious threat to global health.

Study: Farmed fur animals harbour viruses with zoonotic spillover potential. Image Credit: chinahbzyg / Shutterstock

In a recent study published in the journal Nature, researchers conducted a metatranscriptomic investigation of Chinese farmed fur mammals suspected to have died from viral diseases to elucidate if these animals served as a reservoir for viral strains with zoonotic spillover potential. This comprehensive analysis highlights the critical role of fur animals as potential vectors for future pandemics.

Next-generation sequencing of tissues from 461 individual samples collected across 28 species revealed 125 vertebrate-associated virus species from 20 viral families, significantly higher than previously estimated.

Notably, the study identified 36 novel viruses and at least 39 viruses meeting the criteria for high-risk transmission, including seven coronaviruses, depicting cross-species transmission and zoonotic spillover potential. This includes the identification of a novel MERS-like coronavirus in mink and three subtypes of influenza A virus, further expanding the known host range for these pathogens.

The study expanded the known ranges of several virus species and identified previously unknown hosts as disease reservoirs. It highlights mink (reservoir for 23 virus species from 11 viral families), raccoon dogs (19 virus species from 14 viral families), Arctic foxes (13 virus species from 6 viral families), and guinea pigs (potential intermediate host for pathogen transmission) as animals requiring intensive surveillance lest they serve as the trigger for a viral outbreak of pandemic proportions.

Co-infection between different mammalian hosts was observed to be common, with 15 virus species transmitting between fur animals of different orders. For example, the study detected Japanese encephalitis virus in guinea pigs, a virus typically associated with human and swine infections. This finding underscores the broad host spectrum and significant cross-species transmission potential of the identified viruses.

Background

Despite the substantial number of human-specific pathogenic viruses in global circulation, most recent disease outbreaks of epidemic or pandemic proportions (Ebola, SARS, MERS, HIV, Lyme disease, Rift Valley fever, Lassa fever, and COVID-19) have resulted from the zoonotic spillover of their causative agents from animals to humans.

The United Nations Environment Program (UNEP) estimates that 60% of known infectious diseases and 75% of emerging infectious diseases originate in animal reservoirs. This highlights the importance of surveillance and research in preventing the next pandemic event.

Modern advances in viral sequencing technologies have enabled high-throughput pathogen screening of farmed animals, arguably the more frequent source of human disease genesis and transmission.

Unfortunately, most research efforts have hitherto focused on conventional livestock (e.g., cows, goats, and swine), with fur animals (e.g., muskrats, mink, and deer) largely overlooked.

Furthermore, most metagenomic investigations of animal viruses use pooled fecal samples (combining multiple individuals from the same species or location), which, while relevant in diversity and evolutionary analyses, fails to unravel prevalence and co-infection processes.

“…fur animals such as foxes, civets and mink have been suggested to be the potential hosts for a variety of human viruses, including influenza A virus (IAV), SARS-CoV and SARS-CoV-2, and outbreaks of H5N1 IAV have recently been reported in farmed European mink. As humans regularly come into contact with farmed animals, it is critical to improve our knowledge of the viruses that circulate among farmed fur animals and their potential for zoonotic transmission.”

About the study

The present study aims to address current knowledge gaps by individually sampling 461 fur animals from across China (a region historically associated with zoonotic outbreaks yet hitherto understudied) to elucidate animal species at heightened risk of serving as viral reservoirs, thereby guiding future surveillance efforts.

Species were categorized as ‘main’ fur animals (those only farmed for fur and not for food; n = 164 samples from 4 species) and ‘multipurpose’ farmed animals (n = 297 samples from 24 species). Sample collection was carried out between 2021 and 2024 on dead fur mammals suspected of dying from disease.

Sample tissue collection comprised 441 intestinal, 225 lung, and one liver sample. Mitochondrial cytochrome B (Cytb) confirmed the species of fur animals sampled genetically.

The Illumina NovaSeq 6000 platform was used for RNA sequencing, followed by MEGAHIT (v.1.2.8) for the de novo assembly of the rRNA library. Assembled contigs were passed through a non-redundant protein database (Diamond blastx) to identify viruses within the tissue samples. The Bowtie2 platform was used to estimate viral abundance in each sample (metric = reads mapped per million [RPM]).

“We categorized three types of potentially high-risk viruses: (1) a zoonotic virus was defined as a virus that has been found at least once in humans; (2) a cross-order virus was defined as a virus that has not yet been reported to infect humans, but which has been found in two or more animal orders; and (3) a novel potential risk virus was defined as a virus with >60% amino acid similarity to known viruses, where the genus in question has been found in more than three mammalian orders,” the researchers explained.

Study findings

Phylogenetic analysis revealed 125 vertebrate-associated virus species (20 families) across the 461 samples, including 36 previously undescribed species (12 families) absent from the International Committee on Taxonomy of Viruses. Alarmingly, zoonotic viral risk criteria highlighted 13 of these novel species as ‘high-risk,’ emphasizing the need for further research into their epidemiology.

Three hundred thirty-five host samples (>72%) were found positive for at least one virus species, with the study demonstrating a >60% increase in virus host range over previously known. Most fur animal species investigated were found to play host to between 2 and 23 virus species.

Mink, guinea pigs, raccoon dogs, and Arctic foxes were found to be the most generalist hosts, acting as reservoirs for 23, 20, 19, and 13 virus species, respectively.

Of particular concern is the identification of Pipistrellus bat coronavirus HKU5-like viruses in mink, highlighting a cross-order transmission event with significant zoonotic potential. Additionally, novel influenza A viruses, such as H5N6 and H6N2, were detected in mink and muskrat, respectively, indicating these animals could serve as important intermediate hosts in viral transmission chains.

Co-infection between interspecific mammalian hosts was observed to be commonplace – 15 virus species were found to transmit between fur animals of different orders, 11 of which display the potential for zoonotic transmission to humans.

Together, these findings highlight farmed fur animals as significant reservoirs of potential epi- or pandemic-triggering viral pathogens, underscoring the need for extensive surveillance and research efforts to restrict the transmission of these viromes to humans and other domesticated or wild mammalian populations.

“The order Carnivora carried the highest number of potentially high-risk viruses in this study, while guinea pigs (Rodentia) also carried a high diversity of viruses, including JEV and IAV. Guinea pigs may, therefore, act as intermediate hosts in virus transmission chains and warrant more intensive surveillance,” the study concludes.

Conclusions

The present study identified Chinese farmed fur animals (28 species) as unprecedented reservoirs of more than 125 virus species (20 families), 36 novel to science, and at least 13 categorized as ‘high-risk’ for their zoonotic transmission potential to humans.

Furthermore, the study revealed high-priority species (e.g., guinea pigs, muskrats, and mink) and frequent co-infections between mammals and humans, highlighting the need for enhanced surveillance and research to avoid and address future zoonotic outbreaks.

The study’s findings provide crucial reference data for understanding the potential for fur animals to trigger future outbreaks, emphasizing the importance of ongoing virological surveillance to protect public health.