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How Many Mammalian Viruses?

A project that identified almost every virus in the Indian flying fox heralds a new age of viral discovery.

By | September 3, 2013

Indian flying foxWIKIPEDIA, FRITZ GELLER-GRIMMUnfamiliar viruses, such as the SARS and MERS coronaviruses, are hopping into humans from other mammals at an increasing rate. Each new emergence forces researchers into a reactive race, as they try to identify, study, and corral the new viral threats before they can trigger a pandemic.

Now, sick of being caught on the backfoot, one team of scientists is spearheading a new approach to dealing with emerging diseases. The researchers want to catalog every single mammalian virus in the world, before they have a chance to spread to humans. “We need to know how many unknown viruses there are to understand how much of a threat there is,” says study co-leader Peter Daszak from EcoHealth Alliance, a nonprofit conservation organization based on New York. “No one’s been able to do this before.”

Daszak’s team began by counting all the viruses in a single species, the Indian flying fox. Then, they extrapolated to include all 5,500 mammals, estimating that these animals harbor at least 320,000 viruses waiting to be discovered. The figure, while very rough, is meant as a starting point for future research to refine. “We made the edge of the jigsaw puzzle and now we’re working in from that,” said lead author Simon Anthony from Columbia University,  

The figure of 320,000 is also smaller than what most virologists, including Anthony and Daszak, had suspected. “We had this idea that the total diversity of viruses was an inexhaustible, unending pool,” said Anthony. But if his group’s estimates are right, “we could feasibly find most of the viruses that exist in mammals in the next 20 years.” And excepting some avian viruses—like H7N9 influenza—and insect-borne ones—like West Nile virus—the vast majority of emerging diseases hop into humans from other mammals.

“This is very timely, and representative of a new generation of work,” said Nathan Wolfe, a virologist from Stanford University who was not involved with the study. He compared the research to the Framingham Heart Study, which has highlighted the importance of preventive measures that can reduce the risk of heart disease, at a time when most doctors were simply treating it. “I think we’re at the same inflection point in history when it comes to pandemics.”

The team’s strategy was to repeatedly sample the same animal to discover every single virus that lives within it. The flying fox was an obvious choice, as it carries Nipah and Hendra viruses along with many others.

Over five years, a field team led by Jon Epstein and Ariful Islam from EcoHealth Alliance collected almost 1,900 samples of urine, saliva, and feces from flying foxes. “Every sample involved going out at night, catching these very large bats, hauling them down out of nets and anaesthetizing them,” said Daszak. “It was very intensive.”

They amplified and sequenced viral DNA from each sample, and identified 55 distinct viruses from across nine major families. Fifty of these were new to science. As more samples came in, the team noticed that they were discovering new viruses at an ever-slowing rate. Based on this decelerating rate of discovery, and using ecological statistical techniques to estimate populations of wild species, the team calculated that flying foxes probably harbor no more than 58 viruses—just three more than they had found.

If every mammal species has  similar viral diversity, they would collectively harbour 320,000 different viruses. That figure is very preliminary, Daszak noted. “There are plenty of reasons why it could be too low or too high,” he said. For example, the flying fox may harbor many more viruses than the average mammal, as it lives within dense colonies and migrates over long distances. Different mammals could also share many of their viruses, and this overlap would bring the total number down.

“But my gut feeling is that we’re in the right area,” said Daszak. “The actual number will be nearer hundreds of thousands than tens of millions, and that’s far lower than what people have been saying.” The team is now refining its estimate by repeating the study with different mammals, starting with macaques.

The estimate also means that finding all mammalian viruses suddenly becomes a financially feasible goal. Because the flying fox work cost around $1.2 million, the team estimates that it could identify 85 percent of all mammalian viruses for $1.4 billion—a trivial amount compared to the potential cost of pandemics. “The cost of SARS is estimated at $16 billion,” said Wolfe. “What about HIV? You couldn’t come up with the cost of that.”

Nearer term, scientists could examine the new sequences to identify viruses that have the potential to bind receptors on human cells. Researchers could visit places where those viruses exist, check whether people there have undiagnosed illnesses, and see if these are the result of viral spillovers that would otherwise have gone unnoticed. Surveys like this could help to nip nascent outbreaks in the bud, at the point when they are normally invisible to public health.

Anthony, Daszak, and their colleagues  have already begun to do this. Their flying fox studies identified a new virus, called GBV-D, which is related to those that cause hepatitis in humans. The researchers are now searching for people with undiagnosed hepatitis near where they found the virus in Asia, to see whether any of them have been infected by GBV-D. “I think in 20 years, this will be standard operating procedure,” said Daszak.

“They were just using PCR, and nothing fancier,” added Wolfe. “This isn’t only going to be done in ivory tower labs. The exact protocol is being deployed in our laboratories in Cameroon, Gabon, China, Bangladesh, and all over the world.”

“In my lifetime, we might be able to find every mammalian virus that might infect us,” said Daszak. “And once you know your enemies, you can start to do something about them.”

S.J. Anthony et al., “A strategy to estimate unknown viral diversity in mammals,” mBio, e00598-13, 2013.

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Comments

Avatar of: wctopp

wctopp

Posts: 30

September 3, 2013

Butterfly collecting.

Avatar of: Ed Rybicki

Ed Rybicki

Posts: 9

September 4, 2013

Great stuff!  The age of stamp collecting and of discovery is still with us - because there's not a lot of hypothesising involved in this.  Love it!  And while some (eg: wctopp) might criticise the project because it IS just collecting, for the first time we have a realistic estimate of just how many viruses are out there in our mammalian cousins.

And which might get into us, as we increasingly limit their habitats.  Think Ebola; think Marburg, Nipah, Hendra, SARS & MERS - and remember that these things just popped up apparently out of nowhere.  And are all associated with bats, incidentally.

Avatar of: bilekas

bilekas

Posts: 1

September 4, 2013

Mmm... Maybe starting with human viruses would be more relevant? At least if the group says the main objective is human-related. Of course, it is more fun to do the sample collection in India, I supose...

Avatar of: S.Pelech-Kinexus

S.Pelech-Kinexus

Posts: 3

September 6, 2013

 

The estimation of at least 320,000 viruses that can affect mammals is simply based on the identification of 58 unique viruses in flying foxes multiplied by the number of known mammalian species, which was taken as 5,486. Simon Anthony and the other authors of the study acknowledge that this estimate assumes that all mammalian species are targeted by a similar number of viruses and that there is 100% host specificity. However, most viruses appear to be zoonotic and capable of infecting multiple species.

Using an N=1 with the Indian Flying Fox (Pteropus giganteus) as a typical representative of mammals in general is also somewhat tricky as these are extremely mobile and social creatures that reside in high density communities. In coming up with an estimation of viral diversity for a species, the best-studied mammals are actually humans, which admittedly are also atypical. Since 1901, at least 219 viruses have been identified that are capable of infecting humans, and this list has been growing by 3 to 4 new viruses each year (http://rstb.royalsocietypublishing.org/content/367/1604/2864.full).
The ViralZone webpage (http://viralzone.expasy.org/all_by_species/678.html) documents 124 pathogenic viruses that actually cause disease in humans. Of these, 74 (60%) are also found in other animal hosts including insects.

Using the average of the bat and human data, and a 40% host specificity value, the number of viruses than affect mammals can be calculated as equal to approximately 304,000 (=(219+58)/2 x 5,486 x 40%). This is very close to the estimate of at least 320,000 mammalian viruses offered by Simon Anthony and his colleagues at Columbia University.

The International Committee on Taxonomy of Viruses has catalogued a total of 2618 known viruses or viroids that either affect eukaryotes or prokaryotes in their latest list (http://talk.ictvonline.org/files/ictv_documents/m/msl/4440.aspx). The most recent list of known viruses from the Wikipedia: WikiProject Viruses features 3443 distinct viruses (http://en.wikipedia.org/wiki/List_of_viruses). Present knowledge about even the existence of all of the viruses on our planet is evidently extremely limited. Nevertheless, it is remarkable that that only a very tiny subset of the world’s viruses actually cause disease in humans and other mammals. This is perhaps because as a phylum mammals have been around for a much shorter time (i.e. 200 million years) than other vertebrates (over 540 million years), and mammals only really flourished after the demise of the dinosaurs 65 million years ago. Even today, mammals account for less than 0.1% of the biomass on our planet.

The ability of a virus to successfully infect a host requires co-evolution with the host species. Particularly virulent viruses that kill their hosts are not as effective in their propagation. More than half of the known viruses that infect humans cause disease, but the actual number of viruses that can stealthily replicate in humans without obvious evidence of morbidity may number in the multiples more. Future genomic sequencing of human fluid, stool and biopsy specimens will indubitably lead to the identification of much higher numbers of previously unknown human viruses.

Avatar of: Spence

Spence

Posts: 1

September 10, 2013

I love this. Many years ago when I started my doctorate I was also a real bat enthusiast and thought it would be great making a career out of understanding bat viruses. Sadly not post-doc opportunities for such a study were available and I ended up working on human papillomaviris, HIV and influenza viruses. 

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