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The Global Virome Project


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Expanded viral discovery can improve mitigation
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By Dennis Carroll, Peter Daszak,
Nathan D. Wolfe, George F. Gao,
Carlos M. Morel, Subhash Morzaria,
Ariel Pablos-Méndez, Oyewale Tomori,
Jonna A. K. Mazet
Outbreaks of novel and deadly viruses
highlight global vulnerability to
emerging diseases, with many having
massive health and economic impacts.
Our adaptive toolkit—based largely
on vaccines and therapeutics—is often
ineffective because countermeasure develop-
ment can be outpaced by the speed of novel
viral emergence and spread. Following each
outbreak, the public health community be-
moans a lack of prescience, but after decades
of reacting to each event with little focus
on mitigation, we remain only marginally
better protected against the next epidemic.
Our ability to mitigate disease emergence
is undermined by our poor understanding
of the diversity and ecology of viral threats,
and of the drivers of their emergence. We de-
scribe a Global Virome Project (GVP) aimed
to launch in 2018 that will help identify the
bulk of this viral threat and provide timely
data for public health interventions against
future pandemics.
Nearly all recent pandemics have a viral
etiology with animal origins, and with their
intrinsic capacity for interspecies transmis-
sion, viral zoonoses are prime candidates for
causing the next great pandemic (1, 2). How-
ever, if these viruses are our enemy, we do not
yet know our enemy very well. Around 263
viruses from 25 viral families are known to
infect humans (3) (see the figure), and given
the rate of discovery following identification
of the first human virus (yellow fever virus in
1901), it is likely many more will emerge in
the future (4). We estimate, from analysis of
recent viral discovery data (5), that ~1.67 mil-
lion yet-to-be-discovered viral species from
key zoonotic viral families exist in mammal
and bird hosts—the most important reser-
voirs for viral zoonoses (supplementary text).
By analyzing all known viral-host relation-
ships (3, 6), the history of viral zoonoses (7),
and patterns of viral emergence (1), we can
reasonably expect that between 631,000
and 827,000 of these unknown viruses have
zoonotic potential (supplementary text). We
have no readily available technological coun-
termeasures to these as-yet-undiscovered vi-
ruses. Furthermore, the rate of zoonotic viral
spillover into people is accelerating, mirror-
ing the expansion of our global footprint and
travel networks (1, 8), leading to a nonlinear
rise in pandemic risk and an exponential
growth in their economic impacts (8).
Since 2009, the U.S. Agency for International
Development (USAID) has conducted a large-
scale pilot project, spanning more than 35
countries over 8 years at a cost of around
$170 million, to evaluate the feasibility of
preemptively mitigating pandemic threats.
Other previous studies had begun to conduct
targeted viral discovery in wildlife (9), and
develop mitigation strategies for the emer-
gence of avian flu, for example. However, the
USAID Emerging Pandemic Threats (EPT)
PREDICT project is the first global-scale co-
ordinated program designed to conduct vi-
ral discovery in wildlife reservoir hosts, and
characterize ecological and socioeconomic
factors that drive their risk of spillover, to
mitigate their emergence in people (10).
Working with local partners and govern-
ments, wildlife and domestic animals and
at-risk human populations in geographic
hotspots of disease emergence (1) are sam-
pled, and viral discovery conducted. A strat-
egy to identify which novel viruses are most
at risk of spillover has been developed (11),
and further work is conducted on these to
characterize them prior to, or in the early
stages of, spillover. Metadata on the ecology
of wildlife–livestock–human transmission in-
terfaces, and on human behavioral patterns
in communities, are concurrently analyzed
so that strategies to reduce spillover can be
developed (supplementary text). To date,
EPT PREDICT has discovered more than
1000 viruses from viral families that con-
tain zoonoses, including viruses involved in
recent outbreaks (12), and others of ongoing
public health concern (13). The focus of EPT
PREDICT on capacity building, infrastruc-
ture support, training, and epidemiological
analysis differs substantially from the GVP’s
emphasis on large-scale sampling and viral
discovery. However, to discover the bulk of
the projected remaining 1.67 million un-
known viruses in animal reservoirs and char-
acterize the majority of 631,000 to 827,000
viruses of highest zoonotic potential requires
overcoming some challenges of scale.
The first challenge is cost. To estimate this,
we analyzed data on field sampling and labo-
ratory expenditures for viral discovery from
(5, 10), and estimates of unknown viral diver-
sity in mammalian and avian hosts (supple-
mentary text). We estimate that discovery of
all viral threats and characterization of their
risk for spillover, using currently available
technologies and protocols, would be ex-
tremely costly at over $7 billion (supplemen-
tary text). However, previous work shows
that viral discovery rates are vastly higher in
the early stages of a sampling program, and
that discovering the last few, rare, viruses is
extremely costly and time-consuming owing
to the number of samples required to find
The Global Virome Project
Expanded viral discovery can improve mitigation
The list of author affiliations is provided in the supplementary
materials. Email:
POLICY FORUM Scientists prepare to collect a blood sample from
a Rousettus sp. fruit bat in Thailand to test for novel
viruses. The Global Virome Project aims to identify
and characterize the majority of currently unknown
viruses in key wildlife groups, including rodents,
nonhuman primates, and bats.
872 23 FEBRUARY 2018 • VOL 359 ISSUE 6378
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them (5) (supplementary text). We used data
on rates of viral discovery (5) to estimate that
the substantial majority of the viral diversity
from our target zoonotic reservoirs could be
discovered, characterized, and assessed for
viral ecology within a 10-year time frame
for ~$1.2 billion (16% of total costs for 71%
of the virome, considering some fixed costs)
(fig. S1). Those viruses remaining undiscov-
ered will, by the nature of sampling bias to-
ward more common host species, represent
the rarest viruses with least opportunity
for spillover, and therefore reduced public
health risk. Their discovery would require
exponentially greater sampling effort and
funding that could be better spent on coun-
termeasures for the more likely threats (sup-
plementary text).
Stakeholders from Asia, Africa, the
Americas, and Europe, spanning industry,
academia, intergovernmental agencies, non-
governmental organizations (NGOs), and
the private sector, began meeting in 2016
to design a framework for the governance,
management, technical operation, and scope
of the GVP. Key efforts include developing
finance streams; establishing a transparent,
equitable implementation strategy; design-
ing data- and sample-sharing protocols; de-
veloping laboratory and metadata platforms;
targeting of host taxa and sampling sites;
analyzing return on investment; forming
collaborative field and laboratory networks;
developing risk characterization frameworks
for viruses discovered; designing a strategy
to assess and mitigate risk behaviors that
facilitate viral emergence; and planning in-
country capacity building for sustainable
threat mitigation. Funding has been identified
to support an initial administrative hub, and
fieldwork is planned to begin in the first two
countries, China and Thailand, during 2018.
With outputs intended to serve the global
public good, the GVP is developing a transpar-
ent and equitable strategy to share data, viral
samples, and their likely products, including
benefits derived from future development of
medical countermeasures. These build on the
Nagoya Protocol to the Convention on Bio-
logical Diversity and the Pandemic Influenza
Preparedness Framework, negotiated by the
World Health Organization (WHO). The in-
ternational collaborative nature and global
ownership of the project should help leverage
funding from diverse international donors,
including government agencies focused on
national virome projects or on international
development projects in other countries, and
private-sector philanthropic donors focused
on technology and big science.
The diversity of tasks required to conduct
the GVP should reduce the potential for it to
divert funds from current public health pro-
grams. For example, discrete work streams on
targeted sampling of wildlife, on bioinformat-
ics, and on behavioral risk analysis fall within
the focus of current scientific research pro-
grams in a range of donor agencies. Govern-
ments and corporations with specific remits
and geographic responsibilities have been
approached to finance subprojects relevant
to their sectors (e.g., capacity development,
surveillance of specific taxa, geographically
focused activities, medical countermeasure
development, training, surveillance, and
technological platforms). In addition, lead-
ers in China and a number of countries have
begun developing national virome projects as
part of the GVP, leveraging current research
funding to include GVP sites.
Technological challenges include safe field
sampling in remote locations and cost-effec-
tive laboratory platforms that can be stan-
dardized in low-income settings. To achieve
these goals, existing national, regional, and
international networks will need to be en-
hanced and expanded within standardized
sampling and testing frameworks. Existing
networks of field biologists from environ-
ment ministries, academic institutions, and
conservation and health NGOs may assist in
surveillance. National science and technol-
ogy agencies, regional One Health platforms,
transboundary disease surveillance net-
works, Institut Pasteur laboratories, WHO,
United Nations Food and Agricultural Or-
ganization, and the World Organization for
Animal Health collaborating, and reference
centers and viral discovery laboratories, in-
cluding USAID EPT PREDICT, are currently
involved in planning these activities around
a decade-long sampling and testing time
frame. A monitoring and evaluation strat-
egy is being developed based on analysis of
viral discovery rates against predicted viral
diversity, to identify when to halt surveil-
lance and testing as the GVP progresses.
Stakeholders will also tackle the challenge
of how to decide when enough potentially
dangerous viruses have been discovered in a
host species or region to call for action to re-
duce underlying drivers of emergence (e.g.,
hunting and trading of a wildlife reservoir).
Laboratory platforms developed by
USAID EPT PREDICT have proven capacity
to identify novel viruses and are relatively
inexpensive and reliable, being based on
polymerase chain reaction using degenerate
primers that target a range of viral families of
known zoonotic potential. However, scaling
up to a full global virome project will require
discovery of three orders of magnitude more
viruses in a similar time frame. Technologi-
cal solutions will be needed to increase the
speed and efficiency, and reduce the cost,
of sequence generation. These will likely in-
clude next-generation sequencing and other
unbiased approaches to identify evolution-
arily distinct viral clades.
A key challenge is how to assess the po-
tential for novel viruses to infect people or
become pandemic (14). The EPT PREDICT
project (11) and others (2, 6) have developed
preliminary zoonotic risk characterization
frameworks based on viral and host traits and
the ecological and demographic characteris-
tics of the sampling site. These approaches
will be used in the GVP to triage novel viruses
for further characterization to assess their
zoonotic capacity (supplementary text). In vi-
tro receptor binding analyses coupled with in
vivo models have proven useful in this capac-
ity for some viral families [e.g., coronaviruses
(13)]. Although this is not yet feasible for all
potentially zoonotic viral clades, applying
these techniques to a larger viral data set as
the GVP progresses will allow validation of
risk frameworks and may increase our capac-
ity to predict zoonotic potential. However,
advancing these goals will require new col-
laboration among lab virologists, epidemiolo-
gists, and modelers, innovative approaches to
field-testing the boundaries of virus-host re-
lationships, and support across agencies that
often fund separate virology, public health,
evolutionary biology, and biodiversity model-
ing initiatives.
The cost of the GVP represents a sizable
investment and, even if a large number of
potential zoonoses are discovered, only a
minority is likely to have the potential to
cause large-scale outbreaks and mortality in
people (1, 2, 7). However, given the high cost
of single epidemic events, data produced by
the GVP may provide substantial return on
investment by enhancing diagnostic capacity
in the early stages of a new disease outbreak
or by rapidly identifying spillover hosts, for
example. Recent analysis of the exponentially
rising economic damages from increasing
rates of zoonotic disease emergence sug-
gests that strategies to mitigate pandemics
would provide a 10:1 return on investment
(1, 8). Even small reductions in the estimated
costs of a future influenza pandemic (hun-
dreds of billions of dollars) or of the previous
SARS (severe acute respiratory syndrome)
epidemic ($10 billion to $30 billion) could be
substantial. The goal of the GVP is to improve
efficiency in the face of these increasing viral
...the GVP goals…improve
capacity to detect, diagnose,
and discover viruses in
vulnerable populations…
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spillover rates by enhancing (not replacing)
current pandemic surveillance, prevention,
and control strategies. If we were to invest
only in surveillance for known pathogens
(our current business-as-usual strategy), our
calculations suggest we would protect our-
selves against less than 0.1% of those viruses
that could conceivably infect people, even us-
ing the lower bounds of our uncertainty for
our viral estimates (i.e., 263 viruses known
from humans out of 263,824 unknown poten-
tial zoonoses; supplementary text).
The potential benefits of the GVP may be
enhanced to maximize public health benefits
(supplementary text) by (i) optimizing sam-
pling to target species most likely to harbor
“missing zoonoses” (6), or to target emerging
disease hotspot regions most likely to propa-
gate major disease outbreaks (1); (ii) using
human and livestock syndromic surveillance
to identify regions for wildlife sampling prox-
imal to repeated outbreaks of severe influ-
enza-like-illnesses, fevers of unknown origin,
encephalitides, livestock “abortion storms,”
and other potential emerging disease events;
(iii) initially targeting RNA viruses, which
caused 94% of the zoonoses documented
from 1990 to 2010; and (iv) fostering econo-
mies of scale and adoption of technological
innovation as the GVP ramps up. This in-
cludes use of laboratories that can facilitate
regional sample processing, development of
centralized bioinformatics platforms, and
improved logistics for sample collection and
transport. We also expect the cost of testing
and sequencing to decrease as technology
is enhanced, much as the development of
next-generation sequencing reduced genetic
sequencing costs by up to four orders of mag-
nitude in a decade.
The accelerated pace of viral discovery un-
der the GVP will make the virological, phy-
logenetic, and modeling approaches used in
pandemic preparedness more data-rich, and
likely more effective. For example, having the
sequence data for thousands, rather than a
few, viruses from a single family could extend
vaccine, therapeutic, or drug development to
a wider range of targets, leading to broad-
spectrum vaccines and other countermea-
sures. Identification of novel viruses may be
useful to programs like the Coalition for Epi-
demic Preparedness Innovations (CEPI) in
assessing the breadth of action of candidate
vaccines and therapeutics, and in expand-
ing their efficacy. More broad-scale preven-
tion approaches could provide immediate
return on investment prior to vaccine and
countermeasure development, which would
require substantial investment and time. For
example, metadata on viral reservoir host
identity, geography, seasonality, proximity to
people, and drivers of emergence will refine
our mechanistic understanding of spillover
and enhance published models of emerging
infectious diseases risk (1, 6). Identification
of novel viruses in hunted, traded, or farmed
wildlife species could be used to enhance
bio security in markets and farming systems,
reducing public health risk, increasing food
security, and assisting in conservation of
hunted species. The presence of hosts har-
boring high-risk novel viruses in proximity to
human populations may allow targeted fol-
low-up to examine evidence of spillover and
design intervention strategies (supplemen-
tary text). Ultimately, the benefits of the GVP
may include enhancing our understanding of
viral biology, such as drivers of competition
or cooperation among viruses within hosts,
genomic underpinnings of host-virus coevo-
lution, processes underlying deep evolution
of viral clades, and the identification of novel
viral groups (15).
The regions targeted by the GVP are
largely highly biodiverse, rapidly developing
countries in the tropics, which often have low
capacity to deal with public health crises (1).
The expanded laboratory capacity, field sam-
pling, and data generation intrinsic to the
GVP goals will therefore improve capacity
to detect, diagnose, and discover viruses in
vulnerable populations within regions most
critical to preventing future pandemics. This
enhanced capacity may also help improve
diagnosis and control for endemic diseases,
as well as the portion of the virome that re-
mains undiscovered.
The Human Genome Project in the 1980s
catalyzed technological innovation that dra-
matically shortened the time and cost for its
completion, and ushered in the era of per-
sonalized genomics and precision medicine.
The GVP will likely accelerate development
of pathogen discovery technology, diagnos-
tic tests, and science-based mitigation strat-
egies, which may also provide unexpected
benefits. Like the Human Genome Project,
the GVP will provide a wealth of publicly
accessible data, potentially leading to dis-
coveries that are hard to anticipate, per-
haps viruses that cause cancers and chronic
physiological, mental health, or behavioral
disorders. It will provide orders-of-magni-
tude more information about future threats
to global health and biosecurity, improve
our ability to identify vulnerable popula-
tions, and enable us to more precisely target
mitigation and control measures to foster
an era of global pandemic prevention. j
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P.D., N.D.W., and J.A.K.M. are funded by USAID EPT PREDICT.
We ackn owled ge S. J. Ant hony, C. J. Chr isma n, Y. Feferholt z, T.
Gold stein , C. K. John son, D. Na barro, K . J. Olival , N. Ross , E. Rubi n,
R. Waldman, B. Watson, C. Zambrana-Torrelio, attendees of the
Rockefeller Foundation–funded Bellagio Center Global Virome
Project Workshop August 2016 (www.globalviromeproj
about/), members of the GVP Core Group and Steering
Committee, and co-leads of the GVP Working Groups for their
help refining the concept and this manuscript.
Of these 111 viral families,
the GVP will target 25 containing
viruses known to infect
(or to have substantial risk
of infecting) people.
Of these 1.67 million viruses, an
631,00 to 827,000
likely have the capacity to infect
In these 25 families, an estimated
1.67 million unknown viruses
exist in mammals and
birds—hosts that represent 99%
of the risk for viral emergence.
111 viral families have been
discovered globally to date.
874 23 FEBRUARY 2018 • VOL 359 ISSUE 6378
GVP targeting strategy
The project will capitalize on economies of scale
in viral testing, systematically sampling
mammals and birds to identify currently unknown,
potentially zoonotic viruses that they carry.
DA_0223PolicyForum.indd 874 2/21/18 11:05 AM
Published by AAAS
on March 15, 2018 from
The Global Virome Project
Oyewale Tomori and Jonna A. K. Mazet
Dennis Carroll, Peter Daszak, Nathan D. Wolfe, George F. Gao, Carlos M. Morel, Subhash Morzaria, Ariel Pablos-Méndez,
DOI: 10.1126/science.aap7463
(6378), 872-874.359Science
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... Further detailed studies into the molecular, cellular and tissular pathogenesis mechanisms of human viral diseases and also of animal viral diseases with spillover potential are necessary to provide new clues to identify critical points that will be useful in assessing the transmissibility of future outbreaks of known or emerging/re-emerging pathogens. A number of studies have focused on estimating the number of viruses with zoonotic potential circulating in wild animal species [22,267] and even on developing or improving existing prediction models [3,268,269], but often, larger scale functional studies determining com-mon correlates of zoonotic potential for putative emerging viruses for viral glycoproteins or innate immunity antagonism proteins, for example, are lacking. ...
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... The collection and complex network of commensal and pathogenic eukaryotic viruses and bacteriophages termed the virome (Virgin, 2014;Carroll et al., 2018;Ren et al., 2021). Many studies that focused on limited disease types and body compartments suggested an important role of the virome in human physiology and disease (Virgin, 2014;Norman et al., 2015;Li et al., 2019;Liang and Bushman, 2021;Cao et al., 2022). ...
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... The SARS-CoV-2 pandemic has triggered atrocities against bats and presents considerable challenges for bat conservation. More studies on human attitudes towards bats under the current circumstances are warranted as the framing of messages that link bats to the direct transmission of SARS-CoV-2 to humans can foster false beliefs of their role in disease outbreaks and consequently influence the willingness of people to coexist with bats [89][90][91][92][93][94][95]. Reframing this narrative is critical. ...
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Are we prepared to meet the challenge of the next pandemic? Our experience with the current COVID-19 pandemic shows us that even with experts’ predictions and government tabletop exercises, the world’s responses to the outbreak were inadequate. The past 2 years have shown some hurdles that have to be overcome before the next pandemic occurs: controlling the risk of emerging pathogens, improvement of the global health security infrastructure, limiting gain-of-function experiments, addressing the shortage of healthcare workers, and countering misinformation. There are reasons for being hopeful: COVID-19 is still fresh in our memory, advances in vaccine development, the spirit of innovation and collaboration, and more venues for dissemination of scientific information.
Viral metagenomics has contributed enormously to the characterization of a wide range of viruses infecting animals of all phyla in the last decades. Among Neotropical primates, especially those introduced, knowledge about viral diversity remains poorly studied. Therefore, using metagenomics based on virus enrichment, we explored the viral microbiota present in the feces of introduced common marmosets (Callithrix sp.) in three locations from the Silva Jardim region in the State of Rio de Janeiro, Brazil. Fecal samples were collected from nine marmosets, pooled into three sample pools, and sequenced on Illumina MiSeq platform. Sequence reads were analyzed using a viral metagenomic analysis pipeline and two novel insect viruses belonging to the Parvoviridae and Baculoviridae families were identified. The complete genome of a densovirus (Parvoviridae family) of 5,309 nucleotides (nt) was obtained. The NS1 and VP1 proteins share lower than 32% sequence identity with the corresponding proteins of known members of the subfamily Densovirinae. Phylogenetic analysis suggests that this virus represents a new genus, provisionally named Afoambidensovirus due to its discovery in the Brazilian Atlantic Forest. The novel species received the name Afoambidensovirus incertum 1. The complete circular genome of a baculovirus of 107,191 nt was also obtained, showing 60.8% sequence identity with the most closely related member of the Baculoviridae family. Phylogenetic analysis suggests that this virus represents a new species in the Betabaculovirus genus, provisionally named Betabaculovirus incertum 1. In addition, sequences from several families of arthropods in the three pools evaluated were characterized (contigs ranging from 244 to 6,750 nt), corroborating the presence of possible insect hosts with which these new viruses may be associated. Our study expands the knowledge about two viral families known to infect insects, an important component of the marmosets' diet. This identification in hosts' feces samples demonstrates one of the many uses of this type of data and could serve as a basis for future research characterizing viruses in wildlife using noninvasive samples.
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High-throughput sequencing (HTS) and sequence mining tools revolutionized virus detection and discovery in recent years and implementing them with classical plant virology techniques results to a powerful approach to characterize viruses. An example of a virus discovered through HTS is Solanum nigrum ilarvirus 1 (SnIV1) (family Bromoviridae ), which was recently reported in various solanaceous plants from France, Slovenia, Greece, and South Africa. It was likewise detected in grapevines ( Vitaceae ) and several Fabaceae and Rosaceae plant species. Such a very diverse host association is atypical for ilarviruses, thus warranted further investigation. In this study, modern and classical virological tools were combined to accelerate the characterization of SnIV1. Through HTS-based virome surveys, mining of sequence read archive datasets, and literature search, SnIV1 was further identified from diverse plant and non-plant sources globally. SnIV1 isolates showed relatively low variability compared to other phylogenetically related ilarviruses. Phylogenetic analyses showed a distinct basal clade of isolates from Europe, while the rest formed clades of mixed geographic origin. Furthermore, systemic infection of SnIV1 in Solanum villosum and its mechanical and graft transmissibility to solanaceous species were demonstrated. Near identical SnIV1 genomes from the inoculum ( S. villosum ) and inoculated Nicotiana benthamiana were sequenced, thus partially fulfilling Koch’s postulates. SnIV1 was shown to be seed-transmitted and potentially pollen-borne, has spherical virions, and possibly induces histopathological changes in infected N. benthamiana leaf tissues. Overall, this study provided information to better understand the diversity, distribution, and pathobiology of SnIV1, but whether it could emerge as a destructive pathogen remains uncertain. Funding EU Horizon 2020 Marie Skłodowska-Curie Actions Innovative Training Network (H2020 MSCA-ITN) project no. GA 813542 Administration of the Republic of Slovenia for Food Safety, Veterinary Sector and Plant Protection and Slovenian Research Agency (ARRS) funding no. P4-0165, P4-0407, J4-4553 Balik Scientist Program (Republic Act 11035) of the Department of Science and Technology– Philippine Council for Agriculture, Aquatic, and Natural Resources Research and Development (DOST–PCAARRD), Republic of the Philippines The Belgian FPS Health Food Chain Safety and Environment under Project RT18/3 SEVIPLANT
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The study of virus disease emergence, whether it can be predicted and how it might be prevented, has become a major research topic in biomedicine. Here we show that efforts to predict disease emergence commonly conflate fundamentally different evolutionary and epidemiological time scales, and are likely to fail because of the enormous number of unsampled viruses that could conceivably emerge in humans. Although we know much about the patterns and processes of virus evolution on evolutionary time scales as depicted in family-scale phylogenetic trees, these data have little predictive power to reveal the short-term microevolutionary processes that underpin cross-species transmission and emergence. Truly understanding disease emergence therefore requires a new mechanistic and integrated view of the factors that allow or prevent viruses spreading in novel hosts. We present such a view, suggesting that both ecological and genetic aspects of virus emergence can be placed within a simple population genetic framework, which in turn highlights the importance of host population size and density in determining whether emergence will be successful. Despite this framework, we conclude that a more practical solution to preventing and containing the successful emergence of new diseases entails ongoing virological surveillance at the human–animal interface and regions of ecological disturbance.
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The majority of human emerging infectious diseases are zoonotic, with viruses that originate in wild mammals of particular concern (for example, HIV, Ebola and SARS). Understanding patterns of viral diversity in wildlife and determinants of successful cross-species transmission, or spillover, are therefore key goals for pandemic surveillance programs. However, few analytical tools exist to identify which host species are likely to harbour the next human virus, or which viruses can cross species boundaries. Here we conduct a comprehensive analysis of mammalian host-virus relationships and show that both the total number of viruses that infect a given species and the proportion likely to be zoonotic are predictable. After controlling for research effort, the proportion of zoonotic viruses per species is predicted by phylogenetic relatedness to humans, host taxonomy and human population within a species range-which may reflect human-wildlife contact. We demonstrate that bats harbour a significantly higher proportion of zoonotic viruses than all other mammalian orders. We also identify the taxa and geographic regions with the largest estimated number of 'missing viruses' and 'missing zoonoses' and therefore of highest value for future surveillance. We then show that phylogenetic host breadth and other viral traits are significant predictors of zoonotic potential, providing a novel framework to assess if a newly discovered mammalian virus could infect people.
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Although arthropods are important viral vectors, the biodiversity of arthropod viruses, as well as the role that arthropods have played in viral origins and evolution, is unclear. Through RNA sequencing of 70 arthropod species we discovered 112 novel viruses that appear to be ancestral to much of the documented genetic diversity of negative-sense RNA viruses, a number of which are also present as endogenous genomic copies. With this greatly enriched diversity we revealed that arthropods contain viruses that fall basal to major virus groups, including the vertebrate-specific arenaviruses, filoviruses, hantaviruses, influenza viruses, lyssaviruses, and paramyxoviruses. We similarly documented a remarkable diversity of genome structures in arthropod viruses, including a putative circular form, that sheds new light on the evolution of genome organization. Hence, arthropods are a major reservoir of viral genetic diversity and have likely been central to viral evolution.
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Significance With changes in land use and increased urbanization, the frequency with which pathogens jump species barriers to emerge in new hosts is expected to rise. Knowing which viruses may be more likely to become transmissible among humans, as opposed to only generating dead-end spillover infections, would be of considerable benefit to pandemic planning. Using multivariate modeling and multimodel inference, we sought to both identify and quantify those biological features of viruses that best determine interhuman transmissibility. This analysis revealed that chronic, nonsegmented, non–vector-borne, nonenveloped viruses with low host mortality had the highest likelihood of being transmissible among humans whereas genomic features had little predictive power. Our analysis therefore reveals that multiple virological features determine the likelihood of successful emergence.
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Significance Emerging pandemics are increasing in frequency, threatening global health and economic growth. Global strategies to thwart pandemics can be classed as adaptive (reducing impact after a disease emerges) or mitigation (reducing the causes of pandemics). Our economic analysis shows that the optimal time to implement a globally coordinated adaptive policy is within 27 y and that given geopolitical challenges around pandemic control, these should be implemented urgently. Furthermore, we find that mitigation policies, those aimed at reducing the likelihood of an emerging disease originating, are more cost effective, saving between $344.0 billion and $360.8 billion over the next 100 y if implemented today.
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The 2002-3 pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV) was one of the most significant public health events in recent history. An ongoing outbreak of Middle East respiratory syndrome coronavirus suggests that this group of viruses remains a key threat and that their distribution is wider than previously recognized. Although bats have been suggested to be the natural reservoirs of both viruses, attempts to isolate the progenitor virus of SARS-CoV from bats have been unsuccessful. Diverse SARS-like coronaviruses (SL-CoVs) have now been reported from bats in China, Europe and Africa, but none is considered a direct progenitor of SARS-CoV because of their phylogenetic disparity from this virus and the inability of their spike proteins to use the SARS-CoV cellular receptor molecule, the human angiotensin converting enzyme II (ACE2). Here we report whole-genome sequences of two novel bat coronaviruses from Chinese horseshoe bats (family: Rhinolophidae) in Yunnan, China: RsSHC014 and Rs3367. These viruses are far more closely related to SARS-CoV than any previously identified bat coronaviruses, particularly in the receptor binding domain of the spike protein. Most importantly, we report the first recorded isolation of a live SL-CoV (bat SL-CoV-WIV1) from bat faecal samples in Vero E6 cells, which has typical coronavirus morphology, 99.9% sequence identity to Rs3367 and uses ACE2 from humans, civets and Chinese horseshoe bats for cell entry. Preliminary in vitro testing indicates that WIV1 also has a broad species tropism. Our results provide the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV, and that intermediate hosts may not be necessary for direct human infection by some bat SL-CoVs. They also highlight the importance of pathogen-discovery programs targeting high-risk wildlife groups in emerging disease hotspots as a strategy for pandemic preparedness.
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Unlabelled: The majority of emerging zoonoses originate in wildlife, and many are caused by viruses. However, there are no rigorous estimates of total viral diversity (here termed "virodiversity") for any wildlife species, despite the utility of this to future surveillance and control of emerging zoonoses. In this case study, we repeatedly sampled a mammalian wildlife host known to harbor emerging zoonotic pathogens (the Indian Flying Fox, Pteropus giganteus) and used PCR with degenerate viral family-level primers to discover and analyze the occurrence patterns of 55 viruses from nine viral families. We then adapted statistical techniques used to estimate biodiversity in vertebrates and plants and estimated the total viral richness of these nine families in P. giganteus to be 58 viruses. Our analyses demonstrate proof-of-concept of a strategy for estimating viral richness and provide the first statistically supported estimate of the number of undiscovered viruses in a mammalian host. We used a simple extrapolation to estimate that there are a minimum of 320,000 mammalian viruses awaiting discovery within these nine families, assuming all species harbor a similar number of viruses, with minimal turnover between host species. We estimate the cost of discovering these viruses to be ~$6.3 billion (or ~$1.4 billion for 85% of the total diversity), which if annualized over a 10-year study time frame would represent a small fraction of the cost of many pandemic zoonoses. Importance: Recent years have seen a dramatic increase in viral discovery efforts. However, most lack rigorous systematic design, which limits our ability to understand viral diversity and its ecological drivers and reduces their value to public health intervention. Here, we present a new framework for the discovery of novel viruses in wildlife and use it to make the first-ever estimate of the number of viruses that exist in a mammalian host. As pathogens continue to emerge from wildlife, this estimate allows us to put preliminary bounds around the potential size of the total zoonotic pool and facilitates a better understanding of where best to allocate resources for the subsequent discovery of global viral diversity.
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Most pandemics--eg, HIV/AIDS, severe acute respiratory syndrome, pandemic influenza--originate in animals, are caused by viruses, and are driven to emerge by ecological, behavioural, or socioeconomic changes. Despite their substantial effects on global public health and growing understanding of the process by which they emerge, no pandemic has been predicted before infecting human beings. We review what is known about the pathogens that emerge, the hosts that they originate in, and the factors that drive their emergence. We discuss challenges to their control and new efforts to predict pandemics, target surveillance to the most crucial interfaces, and identify prevention strategies. New mathematical modelling, diagnostic, communications, and informatics technologies can identify and report hitherto unknown microbes in other species, and thus new risk assessment approaches are needed to identify microbes most likely to cause human disease. We lay out a series of research and surveillance opportunities and goals that could help to overcome these challenges and move the global pandemic strategy from response to pre-emption.
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Deep sequencing was used to discover a novel rhabdovirus (Bas-Congo virus, or BASV) associated with a 2009 outbreak of 3 human cases of acute hemorrhagic fever in Mangala village, Democratic Republic of Congo (DRC), Africa. The cases, presenting over a 3-week period, were characterized by abrupt disease onset, high fever, mucosal hemorrhage, and, in two patients, death within 3 days. BASV was detected in an acute serum sample from the lone survivor at a concentration of 1.09×10(6) RNA copies/mL, and 98.2% of the genome was subsequently de novo assembled from ∼140 million sequence reads. Phylogenetic analysis revealed that BASV is highly divergent and shares less than 34% amino acid identity with any other rhabdovirus. High convalescent neutralizing antibody titers of >1∶1000 were detected in the survivor and an asymptomatic nurse directly caring for him, both of whom were health care workers, suggesting the potential for human-to-human transmission of BASV. The natural animal reservoir host or arthropod vector and precise mode of transmission for the virus remain unclear. BASV is an emerging human pathogen associated with acute hemorrhagic fever in Africa.
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There are 219 virus species that are known to be able to infect humans. The first of these to be discovered was yellow fever virus in 1901, and three to four new species are still being found every year. Extrapolation of the discovery curve suggests that there is still a substantial pool of undiscovered human virus species, although an apparent slow-down in the rate of discovery of species from different families may indicate bounds to the potential range of diversity. More than two-thirds of human viruses can also infect non-human hosts, mainly mammals, and sometimes birds. Many specialist human viruses also have mammalian or avian origins. Indeed, a substantial proportion of mammalian viruses may be capable of crossing the species barrier into humans, although only around half of these are capable of being transmitted by humans and around half again of transmitting well enough to cause major outbreaks. A few possible predictors of species jumps can be identified, including the use of phylogenetically conserved cell receptors. It seems almost inevitable that new human viruses will continue to emerge, mainly from other mammals and birds, for the foreseeable future. For this reason, an effective global surveillance system for novel viruses is needed.