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Article ; Online: The virus is out of the barn: the emergence of HPAI as a pathogen of avian and mammalian wildlife around the globe.

Runstadler, Jonathan A / Puryear, Wendy B

2024 Volume 85, Issue 5

Abstract: Highly pathogenic avian influenza (HPAI) has persisted as a One Health threat whose current circulation and impact are addressed in the companion Currents in One Health by Puryear and Runstadler, JAVMA, May 2024. Highly pathogenic avian influenza emerged ...

Abstract	Highly pathogenic avian influenza (HPAI) has persisted as a One Health threat whose current circulation and impact are addressed in the companion Currents in One Health by Puryear and Runstadler, JAVMA, May 2024. Highly pathogenic avian influenza emerged as a by-product of agricultural practices and adapted to endemic circulation in wild bird species. Over more than 20 years, continued evolution in a complex ecology involving multiple hosts has produced a lineage that expanded globally over the last 2 years. Understanding the continued evolution and movement of HPAI relies on understanding how the virus is infecting different hosts in different contexts. This includes understanding the environmental factors and the natural ecology of viral transmission that impact host exposure and ultimately evolutionary trajectories. Particularly with the rapid host expansion, increased spillover to mammalian hosts, and novel clinical phenotypes in infected hosts, despite progress in understanding the impact of specific mutations to HPAI viruses that are associated with spillover potential, the threat to public health is poorly understood. Active research is focusing on new approaches to understanding the relationship of viral genotype to phenotype and the implementation of research and surveillance pipelines to make sense of the enormous potential for diverse HPAI viruses to emerge from wild reservoirs amid global circulation.
MeSH term(s)	Animals ; Influenza in Birds/virology ; Influenza in Birds/transmission ; Influenza in Birds/epidemiology ; Animals, Wild/virology ; Birds/virology ; Mammals/virology ; Orthomyxoviridae Infections/veterinary ; Orthomyxoviridae Infections/virology ; Orthomyxoviridae Infections/transmission ; Orthomyxoviridae Infections/epidemiology ; Influenza A virus/pathogenicity ; Influenza A virus/genetics ; Communicable Diseases, Emerging/virology ; Communicable Diseases, Emerging/veterinary ; Communicable Diseases, Emerging/transmission
Language	English
Publishing date	2024-04-13
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	390796-x
ISSN	1943-5681 ; 0002-9645
ISSN (online)	1943-5681
ISSN	0002-9645
DOI	10.2460/ajvr.24.01.0018
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Article ; Online: High-pathogenicity avian influenza in wildlife: a changing disease dynamic that is expanding in wild birds and having an increasing impact on a growing number of mammals.

Puryear, Wendy B / Runstadler, Jonathan A

Journal of the American Veterinary Medical Association

2024 Volume 262, Issue 5, Page(s) 601–609

Abstract: While diverse strains of low-pathogenicity avian influenza have circulated in wild birds for a long period of time, there has previously been little pathology in wild birds, ducks have been the primary and largely asymptomatic wild reservoir, and ... ...

Abstract	While diverse strains of low-pathogenicity avian influenza have circulated in wild birds for a long period of time, there has previously been little pathology in wild birds, ducks have been the primary and largely asymptomatic wild reservoir, and spillover into mammals has been limited and rare. In recent years, a high-pathogenicity avian influenza (HPAI) virus has emerged on the global scene and shifted the previously established dogmas for influenza infection. High-pathogenicity avian influenza has expanded into wildlife in unprecedented numbers and species diversity, with unmatched disease severity for influenza in wildlife. As the disease ecology of influenza has shifted with this new variant, significant efforts are underway to understand disease course, pathology, and species susceptibility. Here we focus primarily on the impact that HPAI has had in wild mammals while framing these novel spillovers within the context of significantly expanding disease in avian species and geography. The clinical and pathology presentations of HPAI in these atypical hosts are discussed, as well as prognosis and risk for continued spillover. The companion Currents in One Health by Runstadler and Puryear, AJVR, May 2024, provides further context on viral reservoirs and possible routes of direct or environmental transmission and risk assessment of viral variants that are emerging within wildlife.
Language	English
Publishing date	2024-04-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	390811-2
ISSN	1943-569X ; 0003-1488
ISSN (online)	1943-569X
ISSN	0003-1488
DOI	10.2460/javma.24.01.0053
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ab Jg. 2022: Lesesaal (EG)

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Article ; Online: A Brief Introduction to Influenza A Virus in Marine Mammals.

Runstadler, Jonathan A / Puryear, Wendy

Methods in molecular biology (Clifton, N.J.)

2020 Volume 2123, Page(s) 429–450

Abstract: Influenza A infection has been detected in marine mammals going back to 1975, with additional unconfirmed outbreaks as far back as 1931. Over the past forty years, infectious virus has been recovered on ten separate occasions from both pinnipeds (harbor ... ...

Abstract	Influenza A infection has been detected in marine mammals going back to 1975, with additional unconfirmed outbreaks as far back as 1931. Over the past forty years, infectious virus has been recovered on ten separate occasions from both pinnipeds (harbor seal, elephant seal, and Caspian seal) and cetaceans (striped whale and pilot whale). Recovered viruses have spanned a range of subtypes (H1, H3, H4, H7, H10, and H13) and, in all but H1N1, show strong evidence for deriving directly from avian sources. To date, there have been five unusual mortality events directly attributed to influenza A virus; these have primarily occurred in harbor seals in the Northeastern United States, with the most recent occurring in harbor seals in the North Sea.There are numerous additional reports wherein influenza A virus has indirectly been identified in marine mammals; these include serosurveillance efforts that have detected influenza A- and B-specific antibodies in marine mammals spanning the globe and the detection of viral RNA in both active and opportunistic surveillance in the Northwest Atlantic. For viral detection and recovery, nasal, rectal, and conjunctival swabs have been employed in pinnipeds, while blowhole, nasal, and rectal swabs have been employed in cetaceans. In the case of deceased animals, virus has also been detected in tissue. Surveillance has historically been somewhat limited, relying largely upon opportunistic sampling of stranded or bycaught animals and primarily occurring in response to a mortality event. A handful of active surveillance projects have shown that influenza may be more endemic in marine mammals than previously appreciated, though live virus is difficult to recover. Surveillance efforts are hindered by permitting and logistical challenges, the absence of reagents and methodology optimized for nonavian wild hosts, and low concentration of virus recovered from asymptomatic animals. Despite these challenges, a growing body of evidence suggests that marine mammals are an important wild reservoir of influenza and may contribute to mammalian adaptation of avian variants.
MeSH term(s)	Animals ; Aquatic Organisms/virology ; Host-Pathogen Interactions ; Humans ; Influenza A virus/isolation & purification ; Influenza A virus/physiology ; Mammals/virology ; Orthomyxoviridae Infections/epidemiology ; Orthomyxoviridae Infections/transmission ; Orthomyxoviridae Infections/virology ; Virus Replication/physiology
Language	English
Publishing date	2020-03-13
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-0346-8_33
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Article ; Online: Influenza virus genotype to phenotype predictions through machine learning: a systematic review.

Borkenhagen, Laura K / Allen, Martin W / Runstadler, Jonathan A

Emerging microbes & infections

2021 Volume 10, Issue 1, Page(s) 1896–1907

Abstract: Background: There is great interest in understanding the viral genomic predictors of phenotypic traits that allow influenza A viruses to adapt to or become more virulent in different hosts. Machine learning techniques have demonstrated promise in ... ...

Abstract	Background: There is great interest in understanding the viral genomic predictors of phenotypic traits that allow influenza A viruses to adapt to or become more virulent in different hosts. Machine learning techniques have demonstrated promise in addressing this critical need for other pathogens because the underlying algorithms are especially well equipped to uncover complex patterns in large datasets and produce generalizable predictions for new data. As the body of research where these techniques are applied for influenza A virus phenotype prediction continues to grow, it is useful to consider the strengths and weaknesses of these approaches to understand what has prevented these models from seeing widespread use by surveillance laboratories and to identify gaps that are underexplored with this technology. Methods and results: We present a systematic review of English literature published through 15 April 2021 of studies employing machine learning methods to generate predictions of influenza A virus phenotypes from genomic or proteomic input. Forty-nine studies were included in this review, spanning the topics of host discrimination, human adaptability, subtype and clade assignment, pandemic lineage assignment, characteristics of infection, and antiviral drug resistance. Conclusions: Our findings suggest that biases in model design and a dearth of wet laboratory follow-up may explain why these models often go underused. We, therefore, offer guidance to overcome these limitations, aid in improving predictive models of previously studied influenza A virus phenotypes, and extend those models to unexplored phenotypes in the ultimate pursuit of tools to enable the characterization of virus isolates across surveillance laboratories.
MeSH term(s)	Algorithms ; Drug Resistance, Viral/genetics ; Genome, Viral/genetics ; Genotype ; Humans ; Influenza A virus/drug effects ; Influenza A virus/genetics ; Influenza A virus/growth & development ; Machine Learning ; Phenotype
Language	English
Publishing date	2021-08-30
Publishing country	United States
Document type	Journal Article ; Systematic Review
ZDB-ID	2681359-2
ISSN	2222-1751 ; 2222-1751
ISSN (online)	2222-1751
ISSN	2222-1751
DOI	10.1080/22221751.2021.1978824
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Article: Bacterial Lipopolysaccharide Destabilizes Influenza Viruses.

Bandoro, Christopher / Runstadler, Jonathan A

mSphere

2017 Volume 2, Issue 5

Abstract: Depending on the specific viral pathogen, commensal bacteria can promote or reduce the severity of viral infection and disease progression in their hosts. Influenza A virus (IAV) has a broad host range, comprises many subtypes, and utilizes different ... ...

Abstract	Depending on the specific viral pathogen, commensal bacteria can promote or reduce the severity of viral infection and disease progression in their hosts. Influenza A virus (IAV) has a broad host range, comprises many subtypes, and utilizes different routes of transmission, including the fecal-oral route in wild birds. It has been previously demonstrated that commensal bacteria can interact with the host's immune system to protect against IAV pathogenesis. However, it is unclear whether bacteria and their products may be interacting directly with IAV to impact virion stability. Herein we show that gastrointestinal (GI) tract bacterial isolates in an
Language	English
Publishing date	2017-09
Publishing country	United States
Document type	Journal Article
ISSN	2379-5042
ISSN	2379-5042
DOI	10.1128/mSphere.00267-17
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Article ; Online: Ecogeographic Drivers of the Spatial Spread of Highly Pathogenic Avian Influenza Outbreaks in Europe and the United States, 2016-Early 2022.

Gass, Jonathon D / Hill, Nichola J / Damodaran, Lambodhar / Naumova, Elena N / Nutter, Felicia B / Runstadler, Jonathan A

International journal of environmental research and public health

2023 Volume 20, Issue 11

Abstract: H5Nx highly pathogenic avian influenza (HPAI) viruses of clade 2.3.4.4 have caused outbreaks in Europe among wild and domestic birds since 2016 and were introduced to North America via wild migratory birds in December 2021. We examined the spatiotemporal ...

Abstract	H5Nx highly pathogenic avian influenza (HPAI) viruses of clade 2.3.4.4 have caused outbreaks in Europe among wild and domestic birds since 2016 and were introduced to North America via wild migratory birds in December 2021. We examined the spatiotemporal extent of HPAI viruses across continents and characterized ecological and environmental predictors of virus spread between geographic regions by constructing a Bayesian phylodynamic generalized linear model (phylodynamic-GLM). The findings demonstrate localized epidemics of H5Nx throughout Europe in the first several years of the epizootic, followed by a singular branching point where H5N1 viruses were introduced to North America, likely via stopover locations throughout the North Atlantic. Once in the United States (US), H5Nx viruses spread at a greater rate between US-based regions as compared to prior spread in Europe. We established that geographic proximity is a predictor of virus spread between regions, implying that intercontinental transport across the Atlantic Ocean is relatively rare. An increase in mean ambient temperature over time was predictive of reduced H5Nx virus spread, which may reflect the effect of climate change on declines in host species abundance, decreased persistence of the virus in the environment, or changes in migratory patterns due to ecological alterations. Our data provide new knowledge about the spread and directionality of H5Nx virus dispersal in Europe and the US during an actively evolving intercontinental outbreak, including predictors of virus movement between regions, which will contribute to surveillance and mitigation strategies as the outbreak unfolds, and in future instances of uncontained avian spread of HPAI viruses.
MeSH term(s)	Animals ; United States/epidemiology ; Influenza in Birds/epidemiology ; Influenza A Virus, H5N1 Subtype ; Bayes Theorem ; Influenza A Virus, H5N2 Subtype ; Disease Outbreaks/veterinary ; Animals, Wild ; Birds ; Influenza A virus ; Europe/epidemiology ; Phylogeny
Language	English
Publishing date	2023-06-01
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2175195-X
ISSN	1660-4601 ; 1661-7827
ISSN (online)	1660-4601
ISSN	1661-7827
DOI	10.3390/ijerph20116030
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Epidemiology and Ecology of Influenza A Viruses among Wildlife in the Arctic

Gass, Jonathon D. / Kellogg, Hunter K. / Hill, Nichola J. / Puryear, Wendy B. / Nutter, Felicia B. / Runstadler, Jonathan A.

Viruses. 2022 July 13, v. 14, no. 7

2022

Abstract: Arctic regions are ecologically significant for the environmental persistence and geographic dissemination of influenza A viruses (IAVs) by avian hosts and other wildlife species. Data describing the epidemiology and ecology of IAVs among wildlife in the ...

Abstract	Arctic regions are ecologically significant for the environmental persistence and geographic dissemination of influenza A viruses (IAVs) by avian hosts and other wildlife species. Data describing the epidemiology and ecology of IAVs among wildlife in the arctic are less frequently published compared to southern temperate regions, where prevalence and subtype diversity are more routinely documented. Following PRISMA guidelines, this systematic review addresses this gap by describing the prevalence, spatiotemporal distribution, and ecological characteristics of IAVs detected among wildlife and the environment in this understudied region of the globe. The literature search was performed in PubMed and Google Scholar using a set of pre-defined search terms to identify publications reporting on IAVs in Arctic regions between 1978 and February 2022. A total of 2125 articles were initially screened, 267 were assessed for eligibility, and 71 articles met inclusion criteria. IAVs have been detected in multiple wildlife species in all Arctic regions, including seabirds, shorebirds, waterfowl, seals, sea lions, whales, and terrestrial mammals, and in the environment. Isolates from wild birds comprise the majority of documented viruses derived from wildlife; however, among all animals and environmental matrices, 26 unique low and highly pathogenic subtypes have been characterized in the scientific literature from Arctic regions. Pooled prevalence across studies indicates 4.23% for wild birds, 3.42% among tested environmental matrices, and seroprevalences of 9.29% and 1.69% among marine and terrestrial mammals, respectively. Surveillance data are geographically biased, with most data from the Alaskan Arctic and many fewer reports from the Russian, Canadian, North Atlantic, and Western European Arctic. We highlight multiple important aspects of wildlife host, pathogen, and environmental ecology of IAVs in Arctic regions, including the role of avian migration and breeding cycles for the global spread of IAVs, evidence of inter-species and inter-continental reassortment at high latitudes, and how climate change-driven ecosystem shifts, including changes in the seasonal availability and distribution of dietary resources, have the potential to alter host–pathogen–environment dynamics in Arctic regions. We conclude by identifying gaps in knowledge and propose priorities for future research.
Keywords	ecosystems ; environmental fate ; influenza ; monitoring ; pathogens ; systematic review ; waterfowl ; wildlife ; Arctic region
Language	English
Dates of publication	2022-0713
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v14071531
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: A Bird's Eye View of Influenza A Virus Transmission: Challenges with Characterizing Both Sides of a Co-Evolutionary Dynamic.

Hill, Nichola J / Runstadler, Jonathan A

Integrative and comparative biology

2016 Volume 56, Issue 2, Page(s) 304–316

Abstract: In nature, wild birds and influenza A viruses (IAV) are continually co-evolving, locked into a back-and-forth of resistance and conquest that has approached a stable equilibrium over time. This co-evolutionary relationship between bird host and IAV may ... ...

Abstract	In nature, wild birds and influenza A viruses (IAV) are continually co-evolving, locked into a back-and-forth of resistance and conquest that has approached a stable equilibrium over time. This co-evolutionary relationship between bird host and IAV may appear stable at the organismal level, but is highly dynamic at the molecular level manifesting in a constant trade-off between transmissibility and virulence of the virus. Characterizing both sides of the host-virus dynamic has presented a challenge for ecologists and virologists alike, despite the potential for this approach to provide insights into which conditions destabilize the equilibrium state resulting in outbreaks or mortality of hosts in extreme cases. The use of different methods that are either host-centric or virus-centric has made it difficult to reconcile the disparate fields of host ecology and virology for investigating and ultimately predicting wild bird-mediated transmission of IAV. This review distills some of the key lessons learned from virological and ecological studies and explores the promises and pitfalls of both approaches. Ultimately, reconciling ecological and virological approaches hinges on integrating scales for measuring host-virus interactions. We argue that prospects for finding common scales for measuring wild bird-influenza dynamics are improving due to advances in genomic sequencing, host-tracking technology and remote sensing data, with the unit of time (months, year, or seasons) providing a starting point for crossover.
MeSH term(s)	Animals ; Birds ; Influenza A virus/genetics ; Influenza A virus/physiology ; Influenza in Birds/immunology ; Influenza in Birds/transmission ; Influenza in Birds/virology
Language	English
Publishing date	2016-06-01
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	2159110-6
ISSN	1557-7023 ; 1540-7063
ISSN (online)	1557-7023
ISSN	1540-7063
DOI	10.1093/icb/icw055
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: A standardized instrument quantifying risk factors associated with bi-directional transmission of SARS-CoV-2 and other zoonotic pathogens: The COVID-19 human-animal interactions survey (CHAIS).

Gass, Jonathon D / Waite, Kaitlin B / Hill, Nichola J / Dalton, Kathryn R / Sawatzki, Kaitlin / Runstadler, Jonathan A / Davis, Meghan F

One health (Amsterdam, Netherlands)

2022 Volume 15, Page(s) 100422

Abstract: Similar to many zoonotic pathogens which transmit from animals to humans, SARS-CoV-2 (CoV-2), the virus responsible for the COVID-19 pandemic, most likely originated in Rhinolophus bats before spreading among humans globally. Early into the pandemic, ... ...

Abstract	Similar to many zoonotic pathogens which transmit from animals to humans, SARS-CoV-2 (CoV-2), the virus responsible for the COVID-19 pandemic, most likely originated in Rhinolophus bats before spreading among humans globally. Early into the pandemic, reports of CoV-2 diagnoses in animals from various countries emerged. While most CoV-2 positive animals were confirmed to have been in close contact with CoV-2 positive humans, there has been a paucity of published evidence to-date describing risk factors associated with CoV-2 transmission among humans and animals. The COVID-19 Human-Animal Interactions Survey (CHAIS) was developed to provide a standardized instrument describing human-animal interactions during the pandemic and to evaluate behavioral, spatiotemporal, and biological risk factors associated with bi-directional zoonotic transmission of CoV-2 within shared environments, predominantly households with limited information about human-wildlife or human-livestock interactions. CHAIS measures four broad domains of transmission risk: 1) risk and intensity of infection in human hosts, 2) spatial characteristics of shared environments, 3) behaviors and human-animal interactions, and 4) susceptible animal subpopulations. Following the development of CHAIS, with a One Health approach, a multidisciplinary group of experts (
Language	English
Publishing date	2022-07-27
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2834831-X
ISSN	2352-7714
ISSN	2352-7714
DOI	10.1016/j.onehlt.2022.100422
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Article ; Online: Epidemiology and Ecology of Influenza A Viruses among Wildlife in the Arctic.

Gass, Jonathon D / Kellogg, Hunter K / Hill, Nichola J / Puryear, Wendy B / Nutter, Felicia B / Runstadler, Jonathan A

Viruses

2022 Volume 14, Issue 7

Abstract	Arctic regions are ecologically significant for the environmental persistence and geographic dissemination of influenza A viruses (IAVs) by avian hosts and other wildlife species. Data describing the epidemiology and ecology of IAVs among wildlife in the arctic are less frequently published compared to southern temperate regions, where prevalence and subtype diversity are more routinely documented. Following PRISMA guidelines, this systematic review addresses this gap by describing the prevalence, spatiotemporal distribution, and ecological characteristics of IAVs detected among wildlife and the environment in this understudied region of the globe. The literature search was performed in PubMed and Google Scholar using a set of pre-defined search terms to identify publications reporting on IAVs in Arctic regions between 1978 and February 2022. A total of 2125 articles were initially screened, 267 were assessed for eligibility, and 71 articles met inclusion criteria. IAVs have been detected in multiple wildlife species in all Arctic regions, including seabirds, shorebirds, waterfowl, seals, sea lions, whales, and terrestrial mammals, and in the environment. Isolates from wild birds comprise the majority of documented viruses derived from wildlife; however, among all animals and environmental matrices, 26 unique low and highly pathogenic subtypes have been characterized in the scientific literature from Arctic regions. Pooled prevalence across studies indicates 4.23% for wild birds, 3.42% among tested environmental matrices, and seroprevalences of 9.29% and 1.69% among marine and terrestrial mammals, respectively. Surveillance data are geographically biased, with most data from the Alaskan Arctic and many fewer reports from the Russian, Canadian, North Atlantic, and Western European Arctic. We highlight multiple important aspects of wildlife host, pathogen, and environmental ecology of IAVs in Arctic regions, including the role of avian migration and breeding cycles for the global spread of IAVs, evidence of inter-species and inter-continental reassortment at high latitudes, and how climate change-driven ecosystem shifts, including changes in the seasonal availability and distribution of dietary resources, have the potential to alter host-pathogen-environment dynamics in Arctic regions. We conclude by identifying gaps in knowledge and propose priorities for future research.
MeSH term(s)	Animals ; Animals, Wild ; Arctic Regions ; Birds ; Canada ; Ecosystem ; Influenza A virus ; Influenza in Birds/epidemiology ; Mammals
Language	English
Publishing date	2022-07-13
Publishing country	Switzerland
Document type	Journal Article ; Review ; Systematic Review ; Research Support, N.I.H., Extramural
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14071531
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