In a Nature Communications article in June 2023 a group of European-based researchers present results of screening for coronaviruses in UK bat species. Collected through a “bat rehabilitation and conservationist network”, 48 faecal samples were screened. Against a background of “limited characterisation” of bat-borne coronaviruses in Europe, the scientists call for “closer surveillance” of the zoonotic risk of the findings, including “two novel coronavirus species” and four “closely related sarbecoviruses” with the potential to, if only “suboptimally” infect human cells.
All a bit familiar
The authors describe the emergence of the COVID-19 pandemic in 2019 as a “sobering reminder of the massive impact of zoonotic viruses on global health and economy”. However, genomic surveillance in wildlife is “limited”. Although careful not to wade too deeply into the origins-of-COVID19 debate, the authors state that SARS-CoV-2 had a “likely evolutionary origin in Rhinolophus bats”. This, coupled with the “subsequent identification of other bat-borne sarbecoviruses in Southeast Asia”, has drawn global attention to the regional risk. However, there is a deliberate emphasis on “more extensive surveillance globally”, as the findings “highlight the zoonotic risk of sarbecoviruses may extend beyond Asia”.
Getting better acquainted with coronaviridae
The authors introduce coronaviridae as a “diverse family of viruses” that can infect a “broad range of animals” and are “prone to zoonotic spillovers”. Although SARS-CoV-2, the “agent of the COVID-19 pandemic” does not have an identified “direct ancestor”, the closest relatives have been isolated from horseshoe bats. Further coronaviruses include SARS-CoV and MERS-CoV, as well as four others that “circulate endemically in humans” with suspected “ancestral reservoirs” being bats and rodents.
The importance of surveillance cannot be overstated, the paper suggests, particularly considering the “current health burden exerted by coronaviruses” and their potential risk as “possible agents of future epidemics and pandemics”. In the study, the authors chose to focus on bats because some human coronaviruses have “ancestral origins” in some of these host species.
Previous research has found a coronavirus prevalence in bats across Asia, Africa, the Middle East, and Europe ranging from 1.5% to 23%. These estimates have most commonly been obtained through reverse transcription PCR (RT-PCR), using degenerate primers to target most species. However, the “vast diversity of coronaviruses” means designing appropriately diverse primers is difficult. Thus, the researchers chose not to use RT-PCR to screen UK bats for coronaviruses, opting instead for a “more accurate estimate of viral diversity and prevalence” in untargeted RNA sequencing.
In the UK there are 17 breeding bat species, which often roost in man-made structures. This “frequent habitat overlap with humans” means that these bats are close to both domesticated and farmed animals, potential bridging hosts for a bat-borne virus. Due to protective law across the UK for all bat species, direct contact with bats is “rare among the general public”. Furthermore, the authors reassuringly state that “multiple factors” are required to align for the “successful emergence of a zoonotic pathogen in humans”. These include:
- Frequency of exposure
- Ability of pathogen to infect humans
- Pathogen capacity for onward human-to-human transmission
Less reassuringly, the authors refer to limited prior research into UK bat coronaviruses, and this was conducted without “direct in vitro assessments of zoonotic risk”. Thus, the “viral diversity and zoonotic potential of UK bat viruses remains largely unknown”, as is true of viruses in “most other UK mammals”.
“Given that the evolutionary origins of many coronaviruses of human health concern can be traced back to bats, assessing their zoonotic potential in UK bats is a top priority.”
Tapping into a bat network
With the existing knowledge gap in mind, the team connected with an existing UK network of bat rehabilitators and conservationists to collect faecal samples from UK bats. This allowed them to secure “geographically and temporally diverse samples”. Excluding the grey long-eared bat, Plecotus austriacus, which is the rarest species in the UK, the team collected and screened faeces from bat species breeding in the UK.
Using deep RNA sequencing they were able to characterise the genomic diversity of bat-borne coronaviruses. Additionally, to assess zoonotic potential, a subset of these coronaviruses was tested for its ability to bind human-cell receptors in vitro.
“We argue this can be a sustainable and effective surveillance model to identify and characterise novel animal-borne viruses that may or may not yet be able to infect humans but might evolve the ability to do so in the future.”
What’s the human threat?
The research indicates that at least one sarbecovirus isolated from the UK horseshoe bats can bind human angiotensin-converting enzyme 2 (hACE2) in vitro. The spike of RhGB07 can use hACE2 for cellular entry. Reassuringly, the authors infer from their findings that the RhGB01-like sarbecoviruses “likely require further adaptations” to make a zoonotic jump.
“Minor adaptations in the spike protein may significantly affect binding affinity with host receptors.
However, a “high prevalence of genetic recombination” amongst sarbecoviruses, particularly in the spike gene, may facilitate viral adaptations to overcome this “genetic barrier for a zoonotic jump”.
“The possibility of a future host jump into humans cannot be ruled out, even if the risk is small.”
The researchers reiterate the need for those in close and frequent contact with bats to observe current biosafety practices. Additionally, they comment on the “important roles” that bats fulfil in global ecosystems. These are threatened by “rapidly declining populations”. Against the backdrop of “human-associated stressors” such as habitat loss, zoonotic spillover can occur.
“It is vitally important that an integrated ecological conservation approach is taken that includes maintaining legal protection, rather than destruction of wildlife and its habitat, in future efforts to mitigate zoonotic risk.”