Virus World

Wildlife is reservoir of emerging viruses. Here we identified 27 families of mammalian viruses from 1981 wild animals and 194 zoo animals collected from south China between 2015 and 2022, isolated and characterized the pathogenicity of eight viruses. Bats harbor high diversity of coronaviruses, picornaviruses and astroviruses, and a potentially novel genus of Bornaviridae. In addition to the reported SARSr-CoV-2 and HKU4-CoV-like viruses, picornavirus and respiroviruses also likely circulate between bats and pangolins. Pikas harbor a new clade of Embecovirus and a new genus of arenaviruses. Further, the potential cross-species transmission of RNA viruses (paramyxovirus and astrovirus) and DNA viruses (pseudorabies virus, porcine circovirus 2, porcine circovirus 3 and parvovirus) between wildlife and domestic animals was identified, complicating wildlife protection and the prevention and control of these diseases in domestic animals. This study provides a nuanced view of the frequency of host-jumping events, as well as assessments of zoonotic risk. Monitoring the diversity of viruses infecting animals is important for assessing zoonotic risk. Here, the authors use metatranscriptomics to characterise the viromes of small mammals, pangolins, and zoo animals in China to identify potentially zoonotic viruses.

Published in Nature Comm. (April 29, 2023):

https://doi.org/10.1038/s41467-023-38202-4 

Early in 2017, a team of medical personnel, including doctors, nurses and volunteers, returned home to Florida after volunteering at a clinic in Haiti. Soon after their return, 20 members of the team began to feel a bit under the weather. "They had a slight fever and didn't feel 100% right," says virologist John Lednicky at the University of Florida. "But they weren't very sick." At the time, Zika virus was circulating in Haiti, and health officials were worried the travelers might have been infected, potentially importing the mosquito-borne illness to Florida. So officials took urine samples from each traveler and asked Lednicky to test for Zika. Lednicky ran the standard PCR tests for the virus, and they all came back negative. But he wasn't satisfied. He had a hunch that the urine samples did contain a virus — not Zika but something else. So he took a little bit of the urine from six of the travelers and added it to a special solution of monkey cells. The goal was deceptively simple: to see if any viruses in the urine would infect the monkey cells, start replicating and grow to detectable levels. Then Lednicky could collect the virus's genes and identify it. "This is what we do in our lab," Lednicky says. "We cast a wide net. We try to isolate viruses. And oftentimes, when we do that, the unexpected happens." Indeed, the unexpected occurred. "We found a coronavirus," he says. And not just any coronavirus, but one that many scientists believe may be a new human pathogen — likely the 8th coronavirus known to cause disease in people. Turns out, this coronavirus in the Haiti travelers has cropped up previously, on the other side of the globe.

Researchers at the University of Duke found mRNA-based vaccines, such as Pfizer and Moderna, induce antibodies that may help fight against coronavirus variants.  The Pfizer and Moderna vaccines are not only effective against COVID-19, but may also help prevent future pandemics. Researchers at Duke University came to this concluding after testing mRNA-based vaccines similar to the jabs used on lab monkeys. According to their findings, which were published in Nature this week, these variety of vaccines induced “broadly neutralizing” antibodies that appeared to protect against Sars-CoV-2—the infection that causes COVID-19—as well as potential variants of coronavirus that could jump from animal to human.  The findings may offer the public a sense of relief as many experts and epidemiologists say there’s a strong chance another pandemic will occur. In an effort to help prevent another outbreak, the team of Duke University researchers developed a pan-coronavirus vaccine that is protein-based rather than mRNA-based. The vaccine was tested on lab animals and showed promising results in fighting the original COVID-19 strain and other variants. Researchers said the vaccine also appeared to stop the virus from replicating in the lungs and nose, which could drastically reduce rates of transmission.

“We began this work last spring with the understanding that, like all viruses, mutations would occur in the SARS-CoV-2 virus,” the study’s senior author Barton F. Haynes, director of the Duke Human Vaccine Institute, said in a press release. “The mRNA vaccines were already under development, so we were looking for ways to sustain their efficacy once those variants appeared. This approach not only provided protection against SARS-CoV-2, but the antibodies induced by the vaccine also neutralized variants of concern that originated in the United Kingdom, South Africa and Brazil. And the induced antibodies reacted with quite a large panel of coronaviruses.”  Dr. Anthony Fauci, the nation’s leading expert in infectious diseases, expressed optimism about Duke’s pan-coronavirus vaccine during a Thursday press conference, saying the next step was to get approval for human trials. “We always have to have a caveat when you’re dealing in a nonhuman primate,” he said, “nonetheless, this is an extremely important proof of concept that we will be aggressively pursuing as we get into the development of human trials,” Fauci said.

Cited study published in Nature (May 10, 2021):

https://doi.org/10.1038/s41586-021-03594-0 

It’s no coincidence that some of the worst viral disease outbreaks in recent years — SARS, MERS, Ebola, Marburg and likely the newly arrived 2019-nCoV virus — originated in bats. A new University of California, Berkeley, study finds that bats’ fierce immune response to viruses could drive viruses to replicate faster, so that when they jump to mammals with average immune systems, such as humans, the viruses wreak deadly havoc. Some bats — including those known to be the original source of human infections — have been shown to host immune systems that are perpetually primed to mount defenses against viruses. Viral infection in these bats leads to a swift response that walls the virus out of cells. While this may protect the bats from getting infected with high viral loads, it encourages these viruses to reproduce more quickly within a host before a defense can be mounted. This makes bats a unique reservoir of rapidly reproducing and highly transmissible viruses. While the bats can tolerate viruses like these, when these bat viruses then move into animals that lack a fast-response immune system, the viruses quickly overwhelm their new hosts, leading to high fatality rates.

“Some bats are able to mount this robust antiviral response, but also balance it with an anti-inflammation response,” said Cara Brook, a postdoctoral Miller Fellow at UC Berkeley and the first author of the study. “Our immune system would generate widespread inflammation if attempting this same antiviral strategy. But bats appear uniquely suited to avoiding the threat of immunopathology.” The researchers note that disrupting bat habitat appears to stress the animals and makes them shed even more virus in their saliva, urine and feces that can infect other animals. “Heightened environmental threats to bats may add to the threat of zoonosis,” said Brook, who works with a bat monitoring program funded by DARPA (the U.S. Defense Advanced Research Projects Agency) that is currently underway in Madagascar, Bangladesh, Ghana and Australia. The project, Bat One Health, explores the link between loss of bat habitat and the spillover of bat viruses into other animals and humans.

“The bottom line is that bats are potentially special when it comes to hosting viruses,” said Mike Boots, a disease ecologist and UC Berkeley professor of integrative biology. “It is not random that a lot of these viruses are coming from bats. Bats are not even that closely related to us, so we would not expect them to host many human viruses. But this work demonstrates how bat immune systems could drive the virulence that overcomes this.”....

Published in Ecology Epidemiology and Global Health (03 February, 2020):

https://doi.org/10.7554/eLife.48401

No other emerging pathogen is known to have jumped so frequently from species to species. A virus that killed a six-year-old boy in 1965 has also infected bonobos and chimpanzees in an unprecedented case of viral ‘ping-pong’ between species.

James Chodosh at Harvard Medical School in Boston, Massachusetts, Donald Seto at George Mason University in Manassas, Virginia, and their colleagues reconstructed the history of a long-stored sample of adenovirus, a type of virus that causes colds and other illnesses. By tracking the small changes that accumulated in the virus’s genome when it infected new species, the researchers found that it had previously lived in bonobos (Pan paniscus), chimpanzees (Pan troglodytes) and humans.

The analysis also showed that the pathogen was remarkably similar to an adenovirus recently identified in two groups of primates that had never come into contact with each other: bonobos in the San Diego Zoo in California and chimpanzees in a primate research facility in Louisiana. The results suggest that the transmission of adenoviruses to humans from other animals might have an important role in the emergence of pathogens that could harm human health.

The original findings were published in the Journal of Virology: https://doi.org/10.1128/JVI.00564-19

We describe animal-to-human transmission of SARS-CoV-2 in a zoo setting in Indiana, USA. A vaccinated African lion with physical limitations requiring hand feeding tested positive for SARS-CoV-2 after onset of respiratory signs. Zoo employees were screened, monitored prospectively for onset of symptoms, then rescreened as indicated; results were confirmed by using reverse transcription PCR and whole-genome virus sequencing when possible. Traceback investigation narrowed the source of infection to 1 of 5 persons. Three exposed employees subsequently had onset of symptoms, 2 with viral genomes identical to the lion’s. Forward contact tracing investigation confirmed probable lion-to-human transmission. Close contact with large cats is a risk factor for bidirectional zoonotic SARS-CoV-2 transmission that should be considered when occupational health and biosecurity practices at zoos are designed and implemented. SARS-CoV-2 rapid testing and detection methods for big cats and other susceptible animals should be developed and validated to enable timely implementation of One Health investigations.

Published (April 17, 2023):

https://doi.org/10.3201/eid2906.230150

Long before COVID-19, scientists had been working to identify animal viruses that could potentially jump to people. These efforts have led to a Web-based platform called SpillOver, which ranks the risk that various viruses will make the leap. Developers hope the new tool will help public health experts and policymakers avoid future outbreaks. Jonna Mazet, an epidemiologist and disease ecologist at the University of California, Davis, has led this work for more than a decade. It began with the USAID PREDICT project, which sought to go beyond well-tracked influenza viruses and identify other emerging pathogens that pose a risk to humans. Thousands of scientists scoured more than 30 countries to locate and identify animal viruses, discovering many new ones in the process. But not every virus is equally threatening. So Mazet and her colleagues decided to create a framework to interpret their findings. “We wanted to move beyond scientific stamp collecting [simply finding viruses] to actual risk evaluation and reduction,” she says. The team was surprised to find very little existing research on categorizing threats from viruses that are currently found only in animals but are in viral families that can likely cause disease in people.

So the researchers started from scratch, identifying 31 factors pertaining to animal viruses (such as how they are transmitted), to their hosts (such as how many and varied they are), and to the environment (human population density, frequency of interaction with hosts, and more). These are summed up in a risk score out of 155; the higher the score, the more likelihood of spillover. Cornell University virologist Colin Parrish, who was not involved in the study, says the factors examined were important in previous spillovers. But he notes that other viruses' crossover risk may be heightened by unforeseeable factors that crop up later. “It's a bit like the stock market,” he says. The new study, published in the Proceedings of the National Academy of Sciences USA, ranks 887 animal-borne viruses. Twelve known human pathogens scored at the top—with the virus that causes COVID-19 in second place, just under the rat-carried Lassa virus. (Influenza would have topped the list if included, Mazet says, but flu variants are already tracked elsewhere.) Parrish notes that the list also omits insect-borne viruses and those from domesticated animals. “This is a work in progress,” he says. “I'm sure it will be iterated into a more powerful tool as more information and data become available. SpillOver is publicly editable, and scientists around the world are already contributing their own findings. Mazet hopes it catches the attention of public health practitioners and leaders, too. With targeted action, Mazet says, “we can ensure that we don't have these spillovers at all. Or if we do, we're ready for them—because we're watching.”

See also research published in P.N.A.S. (April 13, 2021):

https://doi.org/10.1073/pnas.2002324118

An in-depth investigation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks on 16 mink farms by researchers from the Netherlands revealed that minks might serve as a reservoir for persistent infection in humans. The study is currently available on bioRxiv* preprint server. The zoonotic origin of the coronavirus disease pandemic (COVID-19), caused by the SARS-CoV-2, is thus far unknown. Animal experiments have demonstrated that non-human primates, ferrets, cats, rabbits, hamsters and bats can be infected by this virus. A recent introduction to this menagerie is the farmed mink. More specifically, infections in minks were observed in several farms in the Netherlands, while inhalable dust particles in the air of the mink houses were found to harbor SARS-CoV-2 genetic material. The virus was initially diagnosed on two mink farms in the Netherlands on Apr 23 and Apr 25, 2020. After the initial detection of the virus on these farms, an in-depth investigation was initiated to look for potential transmission routes and to conduct an occupational and environmental risk assessment.

In this new study, Dutch researchers from a range of institutions conducted an in-depth investigation into the SARS-CoV-2 outbreak in mink farms and mink farm employees in the Netherlands, combining surveillance data, epidemiological information, and whole-genome sequencing on the human-animal interface. Farm owners at the 16 mink farms positive for SARS-CoV-2 were contacted by the municipal health services in order to conduct the investigation, and their samples were taken for reverse transcription-polymerase chain reaction (RT-PCR) and serological diagnostics. The researchers selected all available near full-length Dutch SARS-CoV-2 genomes in the national database that was available on Jul 1, 2020 (1,775 in total) and aligned with the sequences obtained in this study by using MUSCLE (multiple sequence comparison by log-expectation). Additionally, to discriminate between mink farm-related SARS-CoV-2 infection and locally acquired ones, as well as to ascertain the potential risk for people residing in the proximity of mink farms, whole-genome sequencing was also performed on 34 SARS-CoV-2 positive samples from people who live in the same postal code area.

High sequence diversity of SARS-CoV-2 genomes

This study clearly shows an ongoing SARS-CoV-2 transmission in mink farms, but also pinpoints specific spill-over events to humans. A total of 68% of the tested farmworkers, their relatives, or contacts were shown to be infected with the virus – implying that the contact with SARS-CoV-2-infected mink represents a risk factor for contracting COVID-19. Moreover, phylogenetic analysis of the mink SARS-CoV-2 genomes revealed that mink sequences of 16 farms could be grouped into five different clusters. There were no obvious distinctions in the presentation of disease in animals or humans between clusters based on the currently available data. However, high diversity in the sequences from some mink farms has been observed, likely due to many generations of infected animals before a mortality surge, but possibly also as a result of already circulating virus in specific mink farms...

Preprint available at bioRxiV (Sept. 1, 2020): https://doi.org/10.1101/2020.09.01.277152 

Final version published in Science (Nov. 10, 2020):

https://science.sciencemag.org/content/early/2020/11/09/science.abe5901

Genetic sequences of viruses isolated from the scaly animals are 99% similar to that of the circulating virus — but the work is yet to be formally published. Researchers in Guangzhou, China, have suggested that pangolins — long-snouted, ant-eating mammals often used in traditional Chinese medicine — are the probable animal source of the coronavirus outbreak that has infected more than 30,000 people and is wreaking havoc worldwide. Scientists say that the suggestion, based on a genetic analysis, seems plausible — but caution that the researchers’ work is yet to be published in full. “This is an extremely interesting observation. Although we need to see more details, it does make sense as there are now some other data emerging that pangolins carry viruses that are closely related to 2019-nCoV,” says Edward Holmes, an evolutionary virologist at the University of Sydney, Australia.

The identity of the animal source of the coronavirus, named nCoV-2019, has been one of the key questions that researchers have been racing to answer. Coronaviruses are known to circulate in mammals and birds, and scientists have already suggested that nCoV-2019 originally came from bats, a proposal based on the similarity of its genetic sequence to those of other known coronaviruses. But the virus was probably transmitted to humans by another animal. The coronavirus that caused severe acute respiratory syndrome, or SARS, spread from bats to civet cats to humans. Now, the South China Agricultural University in Guangzhou says that two of its researchers, Shen Yongyi and Xiao Lihua, have identified the pangolin as the potential source of nCoV-2019 on the basis of a genetic comparison of coronaviruses taken from the animals and from humans infected in the outbreak and other findings. The sequences are 99% similar, the researchers reported at press conference on 7 February.

Previously, researchers have noted that coronaviruses are a possible cause of death in pangolins1, and that nCoV-2019 and coronaviruses from pangolins use receptors with similar molecular structures to infect cells. Even before today’s announcement, pangolins were a good candidate for being an intermediate species for the virus, so it’s very interesting that the researchers have found such a close sequence, says David Robertson, a computational virologist at the University of Glasgow, UK....