Once again, the ‘lab leak’ theory of COVID’s origin has returned to the headlines. On Sunday, the Wall Street Journal revealed that a US Department of Energy report had determined that the origin of COVID was ” most likely” an accidental release from a laboratory, according to those who had read the report, though the assessment was with “low confidence”.
Ambassador Nicholas Burns told a US Chamber of Commerce event on Monday that China needs to “be more honest about what happened three years ago in Wuhan with the origin of the Covid-19 crisis”.
China’s foreign ministry countered that COVID’s origin “was about science and should not be politicised”.
The FBI assigned “moderate confidence” to a laboratory origin for the virus, while four other US agencies assigned a “low confidence” to a natural origin. Two others, including the CIA, remained undecided. An update on their views has been provided, apparently due to new information, but has not been made public.
To many scientists, the origin of SARS-CoV-2 has been settled as it has been traced to outbreaks in the Wuhan meat market two weeks before its first detection. A literature analysis published in PNAS concluded that the evidence overwhelmingly favoured a natural origin.
Many other scientists are not convinced by the zoonotic hypothesis. Virologist Jesse Bloom, at the Fred Hutchinson Cancer Center, said the PNAS review’s literature analysis was a good idea – but the zoonosis proponents haven’t provided much new data. “What we’ve seen is mostly reanalysis and reinterpretation of existing evidence.”
The PNAS review started out as a Lancet commission led by Jeffrey Sachs, who disbanded the task force due to a number of members with vested interests against the lab leak hypothesis. Their aim was to gather lessons learnt from the pandemic. The Lancet eventually published its own review, which concluded that there was equal probability for a laboratory or natural origin.
Even so, a continued lack of cooperation from China with international investigators has made it virtually impossible to definitively pinpoint the virus’s emergence. Ultimately, the lesson of past pandemics is that outbreaks can result from either zoonotic origins or from laboratory accidents, both of which are factors which need to be safeguarded against by humans.
The source of the COVID pandemic likely is down to live animals sold at the Huanan Seafood Wholesale Market, according to an international team of researchers.
The researchers traced the start of the pandemic to the market in Wuhan, China, where animals susceptible to the virus were sold live immediately before the pandemic began. Their findings were published in a pair of papers in the journal Science.
The publications all but rule out other explanations for the start of the pandemic, such as the ‘lab leak’ hypothesis. The authors further conclude that the first spread to humans from animals likely occurred in two separate transmission events in the Huanan market in late November 2019.
The first study looked at the locations of the first known COVID cases, as well as swab samples taken various places in the market. The second study examined genomic sequences of SARS-CoV-2 from samples collected from COVID patients during the first weeks of the pandemic in China.
The first paper, led by University of Arizona virus evolution expert Michael Worobey and Professor Kristian Andersen, was able to determine the locations of almost all of the 174 COVID cases identified by the World Health Organization in December 2019, 155 of which were in Wuhan.
A ‘bullseye’ on the market
Analyses showed that these cases were clustered tightly around the Huanan market, whereas later cases were dispersed widely throughout Wuhan. A striking percentage of early COVID patients had not visited there but turned out to live near the market. This suggests that vendors got infected first and set off a chain of infections among community members in the surrounding area, said Worobey.
“In a city covering more than 3000 square miles, the area with the highest probability of containing the home of someone who had one of the earliest COVID cases in the world was an area of a few city blocks, with the Huanan market smack dab inside it,” said Worobey.
This conclusion was supported by another finding: When the authors looked at the geographical distribution of later COVID cases, from January and February 2020, they found a “polar opposite” pattern, Worobey said. While the cases from December 2019 mapped “like a bullseye” on the market, the later cases coincided with areas of the highest population density in Wuhan.
“This tells us the virus was not circulating cryptically,” Worobey said. “It really originated at that market and spread out from there.”
Worobey and collaborators also addressed the question of whether health authorities found cases around the market simply because that is where they looked.
To rule out bias even more, from the market outwards the team removed cases ran the stats again. They found that even when two-thirds of cases were removed, the findings remained the same.
“Even in that scenario, with the majority of cases, removed, we found that the remaining ones lived closer to the market than what would be expected if there was no geographical correlation between these earliest COVID cases and the market,” Worobey said.
The study also looked at swab samples taken from market surfaces like floors and cages after Huanan market was closed. SARS-CoV-2-positive samples were significantly associated with stalls selling live wildlife.
The researchers determined that mammals now known to be susceptible to SARS-CoV-2, including red foxes, hog badgers and raccoon dogs, were sold live at the Huanan market in the weeks preceding the first recorded COVID cases. The scientists developed a detailed map of the market and showed that SARS-CoV-2-positive samples reported by Chinese researchers in early 2020 showed a clear association with the western portion of the market, where live or freshly butchered animals were sold in late 2019.
“Upstream events are still obscure, but our analyses of available evidence clearly suggest that the pandemic arose from initial human infections from animals for sale at the Huanan Seafood Wholesale Market in late November 2019,” said Prof Andersen at Scripps Research, co-senior author of both studies.
Virus likely jumped from animals to humans more than once
The second study, was an analysis of SARS-CoV-2 genomic data from early cases.
The researchers combined epidemic modeling with analyses of the virus’s early evolution based on the earliest sampled genomes. They determined that the pandemic, which initially involved two subtly distinct lineages of SARS-CoV-2, likely arose from at least two separate infections of humans from animals at the Huanan market in November 2019 and perhaps in December 2019. The analyses also suggested that, in this period, there were many other animal-to-human transmissions of the virus at the market that failed to manifest in recorded COVID-19 cases.
Using molecular clock analysis, which relies on the natural pace with which genetic mutations occur over time, researchers established a framework for the evolution of the SARS-CoV-2 virus lineages. They found that a scenario of a singular introduction of the virus into humans rather than multiple introductions would not align with molecular clock data. Earlier studies had suggested that one lineage of the virus – named A and closely related to viral relatives in bats – gave rise to a second lineage, named B. The more likely scenario in which the two lineages jumped from animals into humans on separate occasions, both at the Huanan market, Worobey said.
“Otherwise, lineage A would have had to have been evolving in slow motion compared to the lineage B virus, which just doesn’t make biological sense,” said Worobey.
The two studies provide evidence that COVID originated via jumps from animals to humans at the Huanan market, likely following transmission to those animals from coronavirus-carrying bats in the wild or on farms in China. Moving forward, the researchers say scientists and public officials should seek better understanding of the wildlife trade in China and elsewhere and promote more comprehensive testing of live animals sold in markets to lower the risk of future pandemics.
A new study published in eLife has found that a highly antibiotic-resistant strain of methicillin resistant Staphylococcus aureus (MRSA) has emerged in livestock in the last 50 years, likely a result of widespread antibiotic use in pig farming.
The strain, CC398, has become the dominant type of MRSA in European livestock in the past fifty years. It is also a growing cause of human MRSA infections.
The study found that CC398 has maintained its antibiotic resistance over decades in pigs and other livestock. And it is capable of rapidly adapting to human hosts while maintaining this antibiotic resistance. Increasing numbers of humans have been infected with the strain.
“Historically high levels of antibiotic use may have led to the evolution of this highly antibiotic resistant strain of MRSA on pig farms,” said Dr Gemma Murray, a lead author of the study.
She added: “We found that the antibiotic resistance in this livestock-associated MRSA is extremely stable – it has persisted over several decades, and also as the bacteria has spread across different livestock species.”
Antibiotic use in European livestock is much lower than it has been in the past. But despite policy changes reducing antibiotic use on pig farms, this strain of MRSA in pigs is unlikely to be impacted because it is so stable.
CC398 is found in a range of livestock but mostly in pigs. Its rise has been particularly evident in Danish pig farms where the proportion of MRSA-positive herds has increased from less than 5% in 2008 to 90% in 2018. MRSA doesn’t cause disease in pigs.
“Understanding the emergence and success of CC398 in European livestock – and its capacity to infect humans – is vitally important in managing the risk it poses to public health,” said Dr Lucy Weinert in the University of Cambridge’s Department of Veterinary Medicine, senior author of the paper.
The success of CC398 in livestock and its ability to infect humans is linked to three mobile genetic elements in the MRSA genome. These are chunks of genetic material that give the MRSA certain characteristics, including its resistance to antibiotics and its ability to evade the human immune system.
The researchers reconstructed the evolutionary history of two particular mobile genetic elements called Tn916 and SCCmec that confer antibiotic resistancein MRSA, and found they have persisted in a stable way in CC398 in pigs over decades. They also persist when CC398 jumps to humans — carrying with them high levels of resistance to antibiotics commonly used in farming.
In contrast, a third mobile genetic element called ?Sa3, which enables the CC398 strain of MRSA to evade the human immune system, was found to have frequently disappeared and reappeared over time, in both human-associated and livestock-associated CC398. This suggests that CC398 can rapidly adapt to human hosts.
“Cases of livestock-associated MRSA in humans are still only a small fraction of all MRSA cases in human populations, but the fact that they’re increasing is a worrying sign,” said Weinert.
Intensification of farming, combined with high levels of antibiotic use in livestock, has led to particular concerns about livestock as reservoirs of antibiotic-resistant human infections.
Zinc oxide has been used for many years on pig farms to prevent diarrhoea in piglets. Due to concerns about its environmental impact and its potential promotion of antibiotic resistance in livestock, the European Union will ban its use from this month. But the authors say this ban may not help reduce the prevalence of CC398 because the genes conferring antibiotic resistance are not always linked to the genes that confer resistance to zinc treatment.
Researchers have helped isolate the Lloviu virus (LLOV), a close relative of Ebola virus, for the first time, showing that it could cross over into humans, highlighting the need for future research to ensure pandemic preparedness. The study is reported in Nature Communications.
LLOV is part of the filovirus family, which also includes the Ebola virus. While Ebola (and other filoviruses including the lethal Marburg virus) have only occurred naturally in Africa, Lloviu has been discovered in Europe. The filovirus LLOV, was genetically identified in 2002 in Schreiber’s bats in Spain and was subsequently detected in bats in Hungary.
As a zoonotic virus, LLOV is of public health interest to public health around the world due to our close relationship with animals in agriculture, as companions and in the natural environment. Increasing encroachment on the natural environment is creating more opportunities for zoonotic viruses to cross over into humans.
Dr Simon Scott, from the Viral Pseudotye Unit (VPU) at Medway School of Pharmacy were part of a team led by Dr Gábor Kemenesi from Pécs University/National Laboratory of Virology in Hungary. The VPU were involved in conducting all the antibody detection experiments using bat sera as part of the study, even before the virus itself was isolated. This isolation occurred in the Hungarian lab from the very last bat which tested LLOV positive.
The team discovered that Lloviu has the potential to both infect human cells and replicate, raising concerns about potential widespread transmission in Europe and urges immediate pathogenicity and antiviral studies. The VPU work also revealed no antibody cross-reactivity between LLOV and Ebola, suggesting that existing Ebola vaccines might not protect against Lloviu.
Dr Scott said that their research “is a smoking gun. It’s vital that we know both more about the distribution of this virus and that research is done in this area to assess the risks and to ensure we are prepared for potential epidemics and pandemics.”
The research revealed a considerable knowledge gap regarding the pathogenicity, animal hosts, and transmissibility of these newly discovered viruses. Dr Scott created a consortium of European bat virologists, harnessing expertise in the field, from ecology to virology, which is aiming to carry out essential further research across Europe into the risks of the Lloviu virus to humans.
A previously unknown virus that can infect humans and cause disease has been identified by scientists in Japan. The novel infectious virus, named Yezo virus and transmitted by tick bites, causes a disease characterised by fever and a drop in blood platelets and leucocytes. The discovery was reported in Nature Communications.
Keita Matsuno, a virologist at Hokkaido University’s International Institute for Zoonosis Control, said: “At least seven people have been infected with this new virus in Japan since 2014, but, so far, no deaths have been confirmed.”
The Yezo virus was discovered in 2019 after a 41-year-old man was hospitalised with fever and leg pain after a possible tick bite while walking in a local forest. He was treated and discharged after two weeks, but tests showed he had not been infected with any known viruses carried by ticks in the region. A second patient showed up with similar symptoms after a tick bite the following year.
Genetic analysis of viruses isolated from blood samples of the two patients found a new type of orthonairovirus, a class of nairoviruses. This class includes pathogens such as the Crimean-Congo haemorrhagic fever virus. The scientists named it Yezo virus, after an old name for Hokkaido, the northern Japanese island where the pathogen was discovered. The new virus was found to be closely related to Sulina virus and Tamdy virus, detected in Romania and Uzbekistan, respectively, and recently Tamdy virus reportedly caused acute fever in humans in China.
The researchers then analysed blood samples taken from hospital patients who showed similar symptoms after tick bites since 2014, finding additional positive samples from five patients. These patients, including the first two, had a fever and reduced blood platelets and leucocytes, and showed indicators of abnormal liver function.
To determine the likely source of the virus, the research team screened samples collected from wild animals in the area between 2010 and 2020. They found antibodies for the virus in deer and raccoons and the virus RNA was also found in three major species of ticks in Hokkaido. Matsuno noted that, “The Yezo virus seems to have established its distribution in Hokkaido, and it is highly likely that the virus causes the illness when it is transmitted to humans from animals via ticks.”
As the COVID pandemic has shown, many unknown viruses are present in animal and some can jump to humans. “All of the cases of Yezo virus infection we know of so far did not turn into fatalities, but it’s very likely that the disease is found beyond Hokkaido, so we need to urgently investigate its spread,” said Matsuno.
The research team now plans to determine the distribution of the virus nationwide.
COVID heat map. Photo by Giacomo Carra on Unsplash
A recent article by The Telegraph revealed documents on grant applications by US and Wuhan scientists to conduct coronavirus research in 2018. However, it is important to note that these grants were not funded, and are not direct evidence of a ‘lab leak’ or research-related origin for the coronavirus.
The documents, obtained by a scientist-activist group calling itself DRASTICand confirmed as authentic by a member of the Trump administration, detail grant requests for antigen-bearing nanoparticles and aerosols to be released into bat caves to immunise bat populations. Note that “coronavirus particles” as The Telegraph describes them would be immunising nanoparticles which could describe coronavirus vaccines. Another proposal involved adding “human-specific cleavage sites” to bat coronaviruses to facilitate entry into human cells. The Defense Advanced Research Projects Agency (DARPA) however, refused to fund the work, saying it would have “put local communities at risk.”
What is perhaps more concerning were details of an effort for gain of function research in MERS-CoV, which has a 30% fatality rate, something which an anonymous World Health Organization COVID researcher suggests could have resulted in a pandemic that was “nearly apocalyptic.”
Scientists, however, urge continued impartiality and examining all possibilities, even controversial ones. In an article published on Friday, 24 September in The Lancet, authors point out that there is neither solid evidence for either a natural origin or a for a research origin. In the nineteen months since the beginning of the pandemic, no natural origin has been found despite extensive searching, and independent international researchers do not have access to the investigation sites in China, raw data or samples. However, it took several years for the natural origins of SARS-CoV-1 to be discovered.
They also point out that a research origin for the virus cannot be excluded. Optimisation of the receptor binding domain for human ACE2 could occur through selection or cell cultures, without requiring knowledge of it in advance. Although certain genetic engineering techniques leave signatures in the genome, so-called ‘seamless’ techniques exist.
“On the basis of the current scientific literature, complemented by our own analyses of coronavirus genomes and proteins, we hold that there is currently no compelling evidence to choose between a natural origin (ie, a virus that has evolved and been transmitted to humans solely via contact with wild or farmed animals) and a research-related origin (which might have occurred at sampling sites, during transportation or within the laboratory, and might have involved natural, selected, or engineered viruses).”
SARS-CoV-2 viruses emerging from a human cell. Credit: NIAID
Australian researchers studying SARS-CoV-2 have discovered that the virus is most ideally adapted to infect human cells — instead of bat or pangolin cells, prompting renewed questions about its origin.
The scientists, from Flinders University and La Trobe University, described how they used high-performance computer modelling of SARS-CoV-2’s structure at the beginning of the pandemic to predict its ability to infect humans and a range of 12 domestic and exotic animals.
They were hoping to identify an intermediate animal vector that may have played a role in transmitting a bat virus to humans, and to understand any risk posed by the susceptibilities of pets and livestock.
Using genomic data from 12 animal species, the researchers painstakingly built computer models of the key ACE2 protein receptors for each species. These models were then used to calculate how strongly the SARS-CoV-2 spike protein bound to each species’ ACE2 receptor.
Surprisingly, the results showed that SARS-CoV-2 bound to ACE2 on human cells more tightly than any of the tested animal species, including bats and pangolins. If one of the animal species tested was the origin, it would normally be expected to show the highest binding to the virus.
“Humans showed the strongest spike binding, consistent with the high susceptibility to the virus, but very surprising if an animal was the initial source of the infection in humans,” said Professor David Winkler at La Trobe University.
The findings, originally released on the ArXiv preprint server, have now been peer reviewed and published in Scientific Reports.
“The computer modelling found the virus’s ability to bind to the bat ACE2 protein was poor relative to its ability to bind human cells. This argues against the virus being transmitted directly from bats to humans. Hence, if the virus has a natural source, it could only have come to humans via an intermediary species which has yet to be found,” says Flinders affiliated Professor Nikolai Petrovsky.
The team’s computer modelling also showed fairly strong binding of SARS-CoV-2 to ACE2 from pangolins, which are occasionally used as food or in traditional medicines. Professor Winkler noted that pangolins displayed the highest spike binding energy of all the animals in the study – significantly higher than bats, monkeys and snakes.
“While it was incorrectly suggested early in the pandemic by some scientists that they had found SARS-CoV-2 in pangolins, this was due to a misunderstanding and this claim was rapidly retracted as the pangolin coronavirus they described had less than 90% genetic similarity to SARS-CoV-2 and hence could not be its ancestor,” Prof Petrovsky said.
Similarity in spike proteins
As shown in this and other studies, the specific part of the pangolin coronavirus spike protein that binds to ACE2 was almost identical to its SARS-CoV-2 counterpart.
“This sharing of the almost identical spike protein almost certainly explains why SARS-CoV-2 binds so well to pangolin ACE2. Pangolin and SARS-CoV-2 spike proteins may have evolved similarities through a process of convergent evolution, genetic recombination between viruses, or through genetic engineering, with no current way to distinguish between these possibilities,” Prof Petrovsky said.
“Overall, putting aside the intriguing pangolin ACE2 results, our study showed that the COVID-19 virus was very well adapted to infect humans.”
“We also deduced that some domesticated animals like cats, dogs and cows are likely to be susceptible to SARS-CoV-2 infection too,” Prof Winkler added.
The question of how the virus came to infect humans currently has two main explanations. The virus may have jumped to humans from bats through an intermediary animal which remains to be identified. The other explanation making headlines in the media is an accidental release from a virology lab, where it perhaps was created in ‘gain of function‘ tests, which are carried out around the world to better understand pathogens. A number of organisations and governments, including the World Health Organization and the United States have urged further investigation to find out which of these is correct — though a definitive answer may take years. How and where the SARS-CoV-2 virus adapted to become such an effective human pathogen remains a mystery, the researchers concluded, adding that finding the origins of the disease will help efforts to protect humanity against future coronavirus pandemics.
Journal information: Sakshi Piplani et al, In silico comparison of SARS-CoV-2 spike protein-ACE2 binding affinities across species and implications for virus origin, Scientific Reports (2021). DOI: 10.1038/s41598-021-92388-5
As interest mounts in the ‘lab leak’ hypothesis for the origin of SARS-CoV-2, more scientists are starting to take it seriously, especially because of the important implications of its actual origins.
MedPage Today reported that many experts it approached for the story were hesitant to speculate on its exact implications, they agreed that further research into its origins is important to ward off future pandemics.
A natural origin’s implications
Back in 2007, scientists who were studying coronaviruses warned: “The presence of a large reservoir of SARS-CoV–like viruses in horseshoe bats… is a time bomb. The possibility of the re-emergence of SARS and other novel viruses… should not be ignored.”
On May 26 2021, in the midst of the greatest disaster the world has faced since World War II, US President Joe Biden gave US intelligence 90 days to reach a “definitive conclusion” on the origins of SARS-CoV-2.
Vincent Racaniello, PhD, professor of microbiology and immunology at Columbia University, said finding an answer is unlikely within Biden’s deadline. After all, it took 14 years to find the ancestor of the first SARS virus in wildlife.
For Prof Racaniello, this renewed concern underscores the need for better surveillance of viruses in wildlife.
“All human viruses begin in nature. There’s an overwhelming preponderance of data that shows that, so it makes sense to look in nature when we’re looking for the source of new viruses,” Prof Racaniello told MedPage Today.
As a result of human population pressure, more viruses are spilling over into humans from nature. Examples of this include Ebola, SARS-1, MERS, and bird and swine flu. Because of the evolutionary closeness of mammals and humans, they are major pathogen sources. Rodents and bats (accounting for 20% of mammals), as well as various species of birds are good places to look. However our surveillance of wildlife is spotty, so we have “very little” understanding of the viruses these types of animals harbour, and which ones could be threats to humans, Prof Racaniello warned.
“We need to do more wildlife sampling, to find out what’s out there and what’s potentially a threat,” he said. “More investment in this could have prevented the trillions of dollars that we’ve spent to take care of this pandemic.”
A lab leak’s implications
On the other hand, Richard Ebright, PhD, a molecular biologist and professor of chemistry and chemical biology at Rutgers University in New Jersey, believes the real issue lies in addressing the potential for future pandemics that could originate from lab accidents, a discussion that “needs to begin now.”
“Irrespective of whether COVID originated in a natural accident or a lab accident, the risk of a future pandemic originating in a lab accident is real,” he told MedPage Today.
Prof Ebright explained that, in the US and other countries, only voluntary biosafety guidelines exist, and these are about preventing accidental release of pathogens. While the US has legal regulations against several pathogens that could be used as biological weapons, there are no biosecurity regulations for other pathogens. In most of the world, no biosecurity regulations exist for pathogens other than smallpox, not even voluntary ones, Prof Ebright said.
In 2017, the US implemented a bio-risk policy requiring a risk-benefit analysis before federal funding can be approved for high-risk research, such as ‘gain of function’ research that could be used to increase a pathogen’s transmissibility or pathogenicity to better understand and control it, Prof Ebright said. But this bio-risk policy has been essentially ignored by federal agencies, and the other countries with bio-risk policies only apply it to smallpox.
“Discussion now, especially among policy makers and the public, needs to turn to the inadequacy of biosafety, biosecurity, and biorisk-assessment standards worldwide, and to the essentially complete absence of biosafety regulation worldwide,” he said.
The return of the lab leak hypothesis
While evidence is largely circumstantial, the basic idea is that a laboratory at the Wuhan Institute of Virology had been experimenting on a virus called RaTG13 (a coronavirus closely related to SARS-CoV-2, which infects horseshoe bats), and genetically manipulating other horseshoe bat viruses collected around China. It is thought that one of these laboratory viruses could have infected a staffer at the institute, who then transmitted it to the broader public, Dr Ebright explained.
Following the WHO’s March 30 SARS-CoV-2 origins investigation report, there was a sudden about-face and the lab leak theory began to be taken seriously. Though investigators classified a laboratory origin as “extremely unlikely”, they said the conclusion was reached on the evidence made available.
Even the Director-General of the WHO, Dr Tedros Ghebreyesus, said at the time that he did not believe the assessment of a laboratory origin was “extensive enough,” that this hypothesis “requires further investigation,” and that “this report is a very important beginning, but it is not the end.”
“At this point in time, all scientific data related to the genome sequence of SARS-CoV-2 and the epidemiology of COVID are equally consistent with a natural-accident origin or a laboratory-accident origin,” Ebright said.
While the WHO report does not propose a follow-up study for laboratory origins, it acknowledges that both “follow-up of new evidence” and “regular administrative and internal review of high-level biosafety laboratories worldwide” is needed.
Researchers have, for the first time, detected Zika virus RNA in free-ranging African bats, which indicates that the bats were previously infected with Zika virus at the time the samples were taken.
This discovery also marks the first time scientists have published a study on the detection of Zika virus RNA in any free-ranging bat.
The findings have ecological implications and raise questions about how bats are exposed to Zika virus in the wild. The study was led by Dr Anna Fagre, a veterinary postdoctoral fellow at Colorado State University’s Center for Vector-Borne Infectious Diseases. The findings were detailed in the journal Scientific Reports.
Dr Fagre said that while other studies have shown that bats are susceptible to Zika virus in controlled experimental settings, detection of nucleic acid in bats in the wild indicates that it was transmitted by bites from infected mosquitoes.
“This provides more information about the ecology of flaviviruses and suggests that there is still a lot left to learn surrounding the host range of flaviviruses, like Zika virus,” she said. Other flaviviruses that cause disease in humans include West Nile and dengue.
Wide-ranging samples
Senior author Rebekah Kading, Assistant Professor at CSU, said she, Dr Fagre and the research team were hoping the project would help them to find out more about potential reservoirs of Zika virus.
With 198 samples from bats gathered in the Zika Forest and surrounding areas in Uganda, the team confirmed Zika virus in four bats representing three species. The samples date back as far as 2009 from different parts of Uganda, which is years before the large Zika outbreaks in 2015 to 2017 in North and South America.
The Zika virus was declared a public health emergency by the World Health Organization in February 2016 owing to its association with the congenital deformities, particularly microcephaly in infants borne to the infected mothers
“We knew that flaviviruses were circulating in bats, and we had serological evidence for that,” said Prof Kading. “We wondered: Were bats exposed to the virus or could they have some involvement in transmission of Zika virus?”
The virus detected by the team in the bats was most closely related to the Asian lineage Zika virus, the strain that caused the epidemic in the Americas following outbreaks in Micronesia and French Polynesia. The Asian lineage Zika virus was in late 2016 first detected in Africa, in Angola and Cape Verde.
“Our positive samples, which are most closely related to the Asian lineage Zika virus, came from bats sampled from 2009 to 2013,” said Prof Fagre. “This could mean that the Asian lineage strain of the virus has been present on the African continent longer than we originally thought, or it could mean that there was a fair amount of viral evolution and genomic changes that occurred in African lineage Zika virus that we were not previously aware of.”
Likely incidental hosts, not reservoirs
Prof Fagre said that the relatively low prevalence of Zika virus found indicates that bats may only be incidental hosts of Zika virus infection, rather than amplifying hosts or reservoir hosts.
“Given that these results are from a single cross-sectional study, it would be risky and premature to draw any conclusions about the ecology and epidemiology of this pathogen, based on our study,” she said. “Studies like this only tell one part of the story.”
The research team also made an assay for the study which focuses on subgenomic flavivirus RNA, sfRNA, which flaviviruses possess. Testing for Zika normally uses PCR, polymerase chain reaction, to identify bits of genomic RNA, the nucleic acid that results in the production of protein, said Fagre.
The team’s next steps will be to characterise how long these RNA fragments persist in tissues, which will allow them to estimate how long ago these bats were infected with Zika virus, Prof Kadling said.
“There is always a concern about zoonotic viruses,” she said. “The potential for another outbreak is there and it could go quiet for a while. We know that in the Zika forest, where the virus was first found, the virus is in non-human primates. There are still some questions with that as well. I don’t think Zika virus has gone away forever.”
Journal information: Fagre, A. C., et al. (2021) Subgenomic flavivirus RNA (sfRNA) associated with Asian lineage Zika virus identified in three species of Ugandan bats (family Pteropodidae). Scientific Reports. doi.org/10.1038/s41598-021-87816-5.
A group of experts has argued that trying to survey all of the viruses in the animal kingdom is a futile effort, and that we should rather focus on those most likely to cross over at the interface of humans and animals.
The observation that most of the viruses that cause human disease come from other animals has led some researchers to attempt “zoonotic risk prediction” to second-guess the next virus to cause a global pandemic. Zoonotic viruses, those that cross over from animal species into humans, have caused epidemics and pandemics in humans for centuries. This is exactly what is occurring today with the COVID pandemic: SARS-CoV-2—the coronavirus that causes the disease—emerged from an animal species, albeit which one is not yet known.
An essay published April 20th in the open access journal PLOS Biology, led by Dr Michelle Wille at the University of Sydney, Australia with co-authors Jemma Geoghegan and Edward Holmes outlines the great challenges in zoonotic risk prediction.
The authors argue that these zoonotic risk predictions are of limited value, and will not be able to predict which virus will cause the next great pandemic. Instead, they reason, the human-animal interface should be the target for intensive viral surveillance.
A key question is whether it is possible to predict which animal or which virus group will most likely cause the next pandemic. This has led to “zoonotic risk prediction,” in which researchers attempt to determine which virus families and host groups are most likely to carry potential zoonotic and/or pandemic viruses.
Dr Wille and her colleagues identified several key problems with zoonotic risk prediction attempts.
Firstly, they’re based on very small data sets. Despite decades of work, less than 0.001% of all viruses have likely been identified, even from the mammalian species from which the next pandemic virus is expected to emerge.
Second, these data are also already highly biased in favour of those the most infectious viruses of humans or agricultural animals, or are already known to be zoonotic. Most animals have in fact not been surveyed for viruses, and that viruses evolve so quickly that any such surveys will soon be out of date and therefore be of limited value.
The authors instead argue that a new approach is needed, not trying to futilely survey all the viruses in the wild but instead undertaking extensive sampling at the animal-human interface. This would enable the detection of novel viruses as soon as they appear in humans. This kind of enhanced surveillance could help us forestall the next pandemic.
