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Virome Project Aims to Outfox Pandemics With Global Virus Atlas


NEW YORK (GenomeWeb) – The scourges of Ebola, Zika, HIV, and pandemic influenza each began innocently enough as infections of animals before making the devastating leap into people. A new initiative now aims to eradicate all such zoonotic viral pandemics through a comprehensive characterization of the global virome. 

Blossoming from a predecessor viral discovery project called Predict, which was coordinated by the US Agency for International Development (USAID), the Global Virome Project's lofty goals involve detecting and identifying virtually all potential zoonotic viruses and assembling an atlas that can then help monitor for so-called spillover events. The group proposes that knowing all possible "bad actors" and their ecological niches could lead to refined surveillance programs, detecting incipient outbreaks and heading them off before they can get going.

The GVP itself is an initiative that is currently building momentum and hasn't officially launched, said Jonna Mazet, a member of the GVP steering committee and executive director of the One Health Institute at the University of California, Davis. The institute — a group studying the interactions of animals, humans, and the environment aiming to solve problems that impact health and conservation — also coordinates the Predict project.

"The Predict project provided the feasibility and allowed people to think that it is actually possible to detect viruses and understand the circumstances in which they might spill over prior to an outbreak starting," Mazet said, which created the foundation for the GVP's ambitions. 

Predict is a consortium of global partners and health ministries around the world, and is the surveillance and virus discovery component of USAID's Emerging Pandemic Threats program. It continues to be focused on building capacity to identify potential zoonotic viral threats for locations and activities that are considered high-risk pathogen transmission interfaces between humans and wildlife, where diseases are most likely to emerge. 

The project has been funded by the US Congress since 2009 through a granting mechanism called cooperative agreement between the UC Davis institute and USAID.

In a talk at the recent Association for Molecular Pathology annual meeting, Mazet said that the Predict project has discovered more than 1,000 viruses so far. Only about 20 percent of these were previously known, while about 800 were novel. 

Based on the foundation of the Predict work, which includes around 170 peer-reviewed publications to date, the Global Virome Project hopes to forge ahead with targeted sampling in order to discover more than 99 percent of all zoonotic viruses and create an atlas.

Mazet also said in her talk that there are an estimated 800,000 viruses on the planet that are yet to be discovered, and to find them all would cost maybe $5 billion.

These estimates are based in part on the fact that only 28 viral families have ever had spillover events from animals to humans and caused epidemics, and previously published Predict work has paved the way to estimating viral diversity.

Since its inception, Predict has spent $170 million in 35 countries, Mazet said, training 3,300 people in lab techniques and building 60 labs around the world – sometimes in remote areas adjacent to primeval wilderness, constructed economically out of shipping containers.

The project has also sampled saliva, blood, and feces of more than 74,000 animals, particularly primates, bats, and rodents.

Confidence in the feasibility for GVP is in part based on the viral discovery workflows developed by the Predict project. Mazet said it uses a highly effective conserved-sequence PCR technique for initial viral identification. Setting up the new labs in far-flung places also meant tackling resource limitations and making fresh use of older equipment. "We're certainly helping laboratories get the most out of conventional PCR equipment that they have sitting in the corner," Mazet said.

She said the group regularly compares the conventional PCR to high-throughput genome sequencing on multiple platforms, both for efficiency and also sensitivity to pick up the viruses.

The group also does unbiased sequencing on about a quarter of all samples. Withconventional PCR, the researchers can only discover viruses in viral families that are targeted with the conserved primers, Mazet explained. "We actually get more viruses out of those families that we're looking at with the PCR because it's more sensitive, but we get different viruses [with unbiased sequencing], so together we get a really nice, more complete look," she said.

The group is also moving into using platforms like virCap sequencing and other technologies that combine the very good sensitivity of PCR with the reduction in bias, she said.

In terms of funding, the GVP is still preparing to launch but the original Predict is likely to spend another $40 million or so over the next couple of years, Mazet said. This level of funding has been possible because of a growing understanding of the global losses with each emerging infectious disease outbreak, she said.

"We lose lives and livelihoods — the threat of a Spanish flu, or even a much less severe kind of global flu outbreak, is just almost unfathomable," she said, estimating more than $500 billion dollars a year in cost for a severe worldwide flu pandemic.

"The funding that has been going to science and technology in this realm has been nibbling around at the edges — instead of addressing it in a new way, we keep chasing the last outbreak."

For example, the chances are low that the next big outbreak will be Ebola or Zika, she said, so putting the majority of global resources into studying those viruses won't help get ahead of the next one. 

Interestingly, the Predict project was in place for the recent outbreaks of Ebola and Zika, but happened to not be focusing at the time on the particular regions where those outbreaks occurred.

For Ebola, Mazet said the group's predictive models "exactly highlighted the area of highest risk being right where the spillover event happened in the West Africa outbreak, but at that time, we weren't working in West Africa, we were working in Latin America and East Africa and Southeast Asia."

In the subsequent five-year funding term, USAID added West Africa but removed South America as a region of focus, "so, we were working in West Africa and no longer working in South America when the Zika outbreak came," Mazet said.

The hope is that the Global Virome Project will help in the future. "Instead of focusing on the last region where we just had an outbreak, the world can begin to work together and realize that we're one large ecosystem and we have to be really thinking about these things globally."

Mazet said that right now, most of the data that researchers and public health agencies have to work with is around the known bad actors — the influenzas, Ebolas, SARS, MERS.

"What we need from the Global Virome Project is to identify more of those viruses that might spill over in the future, but also to understand all of the viruses that aren't spilling over," thus delineating factors that enable a virus to leap into people and targeting resources accordingly.  

The factors likely include the genetic piece, Mazet said, "but those are also modulated and driven by the ecological circumstances in which these viruses are occurring and flourishing without causing disease, and the epidemiological circumstances that tell us when they are jumping from species to species help us to identify whether or not they are more likely to be able to jump into people."

An example is ongoing Predict-directed research into bat guano farming. Guano is used as a fertilizer and farming it is becoming a booming business in parts of Southeast Asia. While communities need to be able to live in their environments and have livelihoods, Mazet said, some of the ways that people generate income could be risky to their health.

"We are now aware, because of studies including the Predict project, that bat guano has a lot of virus in it, and a lot of coronavirus in it," she said. Over the last few years, there have been two major outbreaks caused by coronaviruses, including MERS, which is transmitted by camels but has been attributed to a bat-related spillover event.

"If we are aware that an industry is developing and blossoming at the same time that we're learning that what's in that guano is dangerous to human health, how do we attack that tricky problem? We can't without knowledge. We could just go in and tell people, 'don't do that', but they are not going to stop without the knowledge around what part of what they're doing is risky and how risky it is," Mazet said. Ongoing work now focuses on determining whether or not UV irradiation from drying guano in the sun reduces the ability of viruses to get into the food chain.

Overall, to Mazet and the GVP, this work is especially needed because the locales that are often most profoundly affected by a spillover event have fewer resources and weaker health systems. "We have the technology, we have the skills, and we have an obligation as a global community" to do this work, she said.

Mazet said the GVP is now drafting a policy paper that will be featured in an upcoming issue of Science magazine. In addition, in January, about 60 experts from around the world who comprise the GVP steering committee will be convening in Bangkok with support from the government of Thailand to hammer out the next steps for the program.