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Article ; Online: The Ecology of New Constituents of the Tick Virome and Their Relevance to Public Health.

Vandegrift, Kurt J / Kapoor, Amit

2019 Volume 11, Issue 6

Abstract: Ticks are vectors of several pathogens that can be transmitted to humans and their geographic ranges are expanding. The exposure of ticks to new hosts in a rapidly changing environment is likely to further increase the prevalence and diversity of tick- ... ...

Abstract	Ticks are vectors of several pathogens that can be transmitted to humans and their geographic ranges are expanding. The exposure of ticks to new hosts in a rapidly changing environment is likely to further increase the prevalence and diversity of tick-borne diseases. Although ticks are known to transmit bacteria and viruses, most studies of tick-borne disease have focused upon Lyme disease, which is caused by infection with
MeSH term(s)	Animals ; Arachnid Vectors/virology ; Biodiversity ; Borrelia burgdorferi ; Climate Change ; Communicable Diseases, Emerging/virology ; Ecology ; Encephalitis, Tick-Borne ; Flavivirus ; Humans ; Ixodes/virology ; Lyme Disease ; Phlebovirus ; Phylogeny ; Public Health ; Tick-Borne Diseases/transmission ; Tick-Borne Diseases/virology ; Ticks/virology
Language	English
Publishing date	2019-06-07
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v11060529
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Article: The Ecology of New Constituents of the Tick Virome and Their Relevance to Public Health

Vandegrift, Kurt J / Kapoor, Amit

Viruses. 2019 June 07, v. 11, no. 6

2019

Abstract	Ticks are vectors of several pathogens that can be transmitted to humans and their geographic ranges are expanding. The exposure of ticks to new hosts in a rapidly changing environment is likely to further increase the prevalence and diversity of tick-borne diseases. Although ticks are known to transmit bacteria and viruses, most studies of tick-borne disease have focused upon Lyme disease, which is caused by infection with Borrelia burgdorferi. Until recently, ticks were considered as the vectors of a few viruses that can infect humans and animals, such as Powassan, Tick-Borne Encephalitis and Crimean–Congo hemorrhagic fever viruses. Interestingly, however, several new studies undertaken to reveal the etiology of unknown human febrile illnesses, or to describe the virome of ticks collected in different countries, have uncovered a plethora of novel viruses in ticks. Here, we compared the virome compositions of ticks from different countries and our analysis indicates that the global tick virome is dominated by RNA viruses. Comparative phylogenetic analyses of tick viruses from these different countries reveals distinct geographical clustering of the new tick viruses. Some of these new tick RNA viruses (notably severe fever with thrombocytopenia syndrome virus and Heartland virus) were found to be associated with serious human diseases. Their relevance to public health remains unknown. It is plausible that most of these newly identified tick viruses are of endogenous origin or are restricted in their transmission potential, but the efforts to identify new tick viruses should continue. Indeed, future research aimed at defining the origin, the ecology and the spillover potential of this novel viral biodiversity will be critical to understand the relevance to public health.
Keywords	Borrelia burgdorferi ; Lyme disease ; RNA viruses ; bacteria ; biodiversity ; fever ; geographical distribution ; hosts ; human diseases ; humans ; pathogens ; phylogeny ; public health ; thrombocytopenia ; tick-borne encephalitis ; ticks ; viruses
Language	English
Dates of publication	2019-0607
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v11060529
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Article ; Online: A molecular reconstruction of holarctic Heligmosomidae reveals a new species of Heligmosomoides (Nematoda: Heligmosomidae) in Peromyscus maniculatus (Neotominae) from Canada

Alnaqeb, Haitham / Greiman, Stephen E. / Vandegrift, Kurt J. / Campbell, Mariel L. / Meagher, Shawn / Jiménez-Ruiz, F. Agustín

Systematics and Biodiversity. 2022 Dec. 31, v. 20, no. 1 p.1-19

2022

Abstract: A new species of Heligmosomoides Hall, 1916 is proposed for nematodes collected from deer mice, Peromyscus maniculatus, in western Canada. The unequivocal diagnostic character for this species is the presence of two internal bursal membranes. Only four ... ...

Abstract	A new species of Heligmosomoides Hall, 1916 is proposed for nematodes collected from deer mice, Peromyscus maniculatus, in western Canada. The unequivocal diagnostic character for this species is the presence of two internal bursal membranes. Only four species, Heligmosomoides bullosus, Heligmosomoides douglasi, Heligmosomoides montanus and Heligmosomoides vandegrifti, are characterized as possessing a single internal bursal membrane. The genetic distance between Heligmosomoides bibullosus sp. nov., and its putative sister clade Heligmosomoides vandegrifti is congruent with their geographic separation by the mountain range of the Rockies and 4000 km; both morphological difference as well as geography and genetic distance suggest isolation among the two species. Further, H. bibullosus sp. nov. infects deer mice (P. maniculatus) whereas H. vandegrifti is frequently collected in white-footed mice (P. leucopus). Finally, this study supports the taxonomic importance of the monodelphic/didelphic condition as a diagnostic trait within the family, the paraphyly of Heligmosomoides, and reveals undocumented diversity of Heligmosomoides in Nearctic rodents of the Neotominae. The present taxon is the third species in members of this subfamily of rodents. http://www.zoobank.org/urn:lsid:zoobank.org:pub:DE78368D-2CDE-4F9D-AB85-A3CE20D957F4
Keywords	Heligmosomoides ; Nearctic region ; Peromyscus maniculatus ; biodiversity ; deer ; genetic distance ; geography ; mountains ; new species ; paraphyly ; Canada ; Rocky Mountain region ; Heligmosomoides, Heligmosomoides bibullosus ; Nematoda ; Heligmosomoidea ; museum research ; Yukon Territory ; British Columbia
Language	English
Dates of publication	2022-1231
Size	p. 1-19.
Publishing place	Taylor & Francis
Document type	Article ; Online
ZDB-ID	2110629-0
ISSN	1478-0933 ; 1477-2000
ISSN (online)	1478-0933
ISSN	1477-2000
DOI	10.1080/14772000.2022.2046199
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Article: A CNN model for predicting binding affinity changes between SARS-CoV-2 spike RBD variants and ACE2 homologues.

Chen, Chen / Boorla, Veda Sheersh / Chowdhury, Ratul / Nissly, Ruth H / Gontu, Abhinay / Chothe, Shubhada K / LaBella, Lindsey / Jakka, Padmaja / Ramasamy, Santhamani / Vandegrift, Kurt J / Nair, Meera Surendran / Kuchipudi, Suresh V / Maranas, Costas D

bioRxiv : the preprint server for biology

2022

Abstract: The cellular entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) involves the association of its receptor binding domain (RBD) with human angiotensin converting enzyme 2 (hACE2) as the first crucial step. Efficient and reliable ... ...

Abstract	The cellular entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) involves the association of its receptor binding domain (RBD) with human angiotensin converting enzyme 2 (hACE2) as the first crucial step. Efficient and reliable prediction of RBD-hACE2 binding affinity changes upon amino acid substitutions can be valuable for public health surveillance and monitoring potential spillover and adaptation into non-human species. Here, we introduce a convolutional neural network (CNN) model trained on protein sequence and structural features to predict experimental RBD-hACE2 binding affinities of 8,440 variants upon single and multiple amino acid substitutions in the RBD or ACE2. The model achieves a classification accuracy of 83.28% and a Pearson correlation coefficient of 0.85 between predicted and experimentally calculated binding affinities in five-fold cross-validation tests and predicts improved binding affinity for most circulating variants. We pro-actively used the CNN model to exhaustively screen for novel RBD variants with combinations of up to four single amino acid substitutions and suggested candidates with the highest improvements in RBD-ACE2 binding affinity for human and animal ACE2 receptors. We found that the binding affinity of RBD variants against animal ACE2s follows similar trends as those against human ACE2. White-tailed deer ACE2 binds to RBD almost as tightly as human ACE2 while cattle, pig, and chicken ACE2s bind weakly. The model allows testing whether adaptation of the virus for increased binding with other animals would cause concomitant increases in binding with hACE2 or decreased fitness due to adaptation to other hosts.
Language	English
Publishing date	2022-03-23
Publishing country	United States
Document type	Preprint
DOI	10.1101/2022.03.22.485413
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Article ; Online: Presence of Segmented Flavivirus Infections in North America

Vandegrift, Kurt J / Kumar, Arvind / Sharma, Himanshu / Murthy, Satyapramod / Kramer, Laura D / Ostfeld, Richard / Hudson, Peter J / Kapoor, Amit

Emerging infectious diseases

2020 Volume 26, Issue 8, Page(s) 1810–1817

Abstract: Identifying viruses in synanthropic animals is necessary for understanding the origin of many viruses that can infect humans and developing strategies to prevent new zoonotic infections. The white-footed mouse, Peromyscus leucopus, is one of the most ... ...

Abstract	Identifying viruses in synanthropic animals is necessary for understanding the origin of many viruses that can infect humans and developing strategies to prevent new zoonotic infections. The white-footed mouse, Peromyscus leucopus, is one of the most abundant rodent species in the northeastern United States. We characterized the serum virome of 978 free-ranging P. leucopus mice caught in Pennsylvania. We identified many new viruses belonging to 26 different virus families. Among these viruses was a highly divergent segmented flavivirus whose genetic relatives were recently identified in ticks, mosquitoes, and vertebrates, including febrile humans. This novel flavi-like segmented virus was found in rodents and shares ≤70% aa identity with known viruses in the highly conserved region of the viral polymerase. Our data will enable researchers to develop molecular reagents to further characterize this virus and its relatives infecting other hosts and to curtail their spread, if necessary.
MeSH term(s)	Animals ; Flavivirus/genetics ; Flavivirus Infections/epidemiology ; Flavivirus Infections/veterinary ; Mice ; New England ; North America/epidemiology ; Pennsylvania/epidemiology
Keywords	covid19
Language	English
Publishing date	2020-07-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1380686-5
ISSN	1080-6059 ; 1080-6040
ISSN (online)	1080-6059
ISSN	1080-6040
DOI	10.3201/eid2608.190986
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Article ; Online: Could parasites destabilize mouse populations? The potential role of Pterygodermatites peromysci in the population dynamics of free-living mice, Peromyscus leucopus.

Vandegrift, Kurt J / Hudson, Peter J

International journal for parasitology

2009 Volume 39, Issue 11, Page(s) 1253–1262

Abstract: Peromyscus leucopus populations exhibit unstable population dynamics. Mathematical models predict instability with chronic parasite infections that reduce host fecundity when the parasite distribution within the host population is close to random. We ... ...

Abstract	Peromyscus leucopus populations exhibit unstable population dynamics. Mathematical models predict instability with chronic parasite infections that reduce host fecundity when the parasite distribution within the host population is close to random. We examined the role the nematode Pterygodermatites peromysci may play in influencing the dynamics of these mice. There were seven gastrointestinal worms infecting mice. Pterygodermatites peromysci was the most prevalent and varied seasonally from 12.3% in November to 36.0% in July. Prevalence was higher in adults (30.8%) than juveniles (4.6%) and there were no statistical differences in prevalence or intensity between the sexes. Overall the distribution was random; the relationship between log variance and log mean of P. peromysci intensity from 17 sites was not significantly different from unity. There were significant relationships between infection and breeding condition, suggesting parasites could be the cause of reduced female breeding. A generalized linear model found the likelihood of P. peromysci infection in adults increased with body mass, the presence of other helminths, and when hosts were in breeding condition. Likewise, the intensity of infection was positively related to co-infections and body mass. Pterygodermatites peromysci infection was associated with the presence of the oxyurid nematode Syphacia peromysci but co-infection was lower in females than males. Amongst females, co-infection was greater when breeding, particularly during lactation. The P. peromysci age-intensity relationship increased with age and rose to an asymptote as expected for a parasite with constant mortality and no acquired immunity. Overall, P. peromysci had a random distribution and was associated with reduced breeding; we discuss how these destabilizing processes may influence the dynamics of P. leucopus.
MeSH term(s)	Age Factors ; Animals ; Disease Reservoirs/parasitology ; Female ; Helminthiasis, Animal/complications ; Helminthiasis, Animal/epidemiology ; Host-Parasite Interactions ; Lactation ; Male ; Nematoda/physiology ; North America ; Peromyscus/parasitology ; Peromyscus/physiology ; Platyhelminths/parasitology ; Population Density ; Population Dynamics ; Pregnancy ; Prevalence ; Reproduction/physiology ; Rodent Diseases/epidemiology ; Seasons
Language	English
Publishing date	2009-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	120518-3
ISSN	1879-0135 ; 0020-7519
ISSN (online)	1879-0135
ISSN	0020-7519
DOI	10.1016/j.ijpara.2009.02.025
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Article ; Online: Peromyscus as a model system for human hepatitis C: An opportunity to advance our understanding of a complex host parasite system.

Vandegrift, Kurt J / Critchlow, Justin T / Kapoor, Amit / Friedman, David A / Hudson, Peter J

Seminars in cell & developmental biology

2017 Volume 61, Page(s) 123–130

Abstract: Worldwide, there are 185 million people infected with hepatitis C virus and approximately 350,000 people die each year from hepatitis C associated liver diseases. Human hepatitis C research has been hampered by the lack of an appropriate in vivo model ... ...

Abstract	Worldwide, there are 185 million people infected with hepatitis C virus and approximately 350,000 people die each year from hepatitis C associated liver diseases. Human hepatitis C research has been hampered by the lack of an appropriate in vivo model system. Most of the in vivo research has been conducted on chimpanzees, which is complicated by ethical concerns, small sample sizes, high costs, and genetic heterogeneity. The house mouse system has led to greater understanding of a wide variety of human pathogens, but it is unreasonable to expect Mus musculus to be a good model system for every human pathogen. Alternative animal models can be developed in these cases. Ferrets (influenza), cotton rats (human respiratory virus), and woodchucks (hepatitis B) are all alternative models that have led to a greater understanding of human pathogens. Rodent models are tractable, genetically amenable and inbred and outbred strains can provide homogeneity in results. Recently, a rodent homolog of hepatitis C was discovered and isolated from the liver of a Peromyscus maniculatus. This represents the first small mammal (mouse) model system for human hepatitis C and it offers great potential to contribute to our understanding and ultimately aid in our efforts to combat this serious public health concern. Peromyscus are available commercially and can be used to inform questions about the origin, transmission, persistence, pathology, and rational treatment of hepatitis C. Here, we provide a disease ecologist's overview of this new virus and some suggestions for useful future experiments.
Language	English
Publishing date	2017-01
Publishing country	England
Document type	Review ; Journal Article
ZDB-ID	1312473-0
ISSN	1096-3634 ; 1084-9521
ISSN (online)	1096-3634
ISSN	1084-9521
DOI	10.1016/j.semcdb.2016.07.031
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Article ; Online: Response to enrichment, type and timing: small mammals vary in their response to a springtime cicada but not a carbohydrate pulse.

Vandegrift, Kurt J / Hudson, Peter J

The Journal of animal ecology

2009 Volume 78, Issue 1, Page(s) 202–209

Abstract: 1. Masting events in the autumn provide a carbohydrate-rich pulse of resources that can influence the dynamics of small mammals and their natural enemies. Similar patterns are observed with the periodical cicada emergence which provides a protein-rich ... ...

Abstract	1. Masting events in the autumn provide a carbohydrate-rich pulse of resources that can influence the dynamics of small mammals and their natural enemies. Similar patterns are observed with the periodical cicada emergence which provides a protein-rich pulse in the spring, but comparisons are confounded by timing and food type. 2. We compared the influence of a naturally occurring spring pulse of cicadas with an experimental spring pulse of carbohydrate-rich seeds. We used a replicated population level field experiment and capture-mark-recapture techniques to record the vital rates, demographics, and abundance of Peromyscus leucopus (the white-footed mouse), as well as other small mammals and their parasites. 3. The density of P. leucopus on grids where cicadas emerged was 55% higher than controls as a consequence of early breeding. This was followed by an increase in the prevalence of the nematode Pterygodermatities peromysci, reduced breeding and decreased recruitment rates. Other small mammals including Tamias striatus (eastern chipmunk) and Blarina brevicauda (short-tailed shrew), increased in density, but there was no affect on Sorex cinereus (masked shrew). 4. In contrast to the presence of cicadas, there was no influence of sunflower seed supplementation on small mammal density, vital rates, or reproduction with the exception of an increase in B. brevicauda density. The response of small mammals to seasonal pulses depends on timing, food type, and species.
MeSH term(s)	Animals ; Dietary Carbohydrates/metabolism ; Female ; Hemiptera/physiology ; Intestines/parasitology ; Male ; Mice ; Nematoda/physiology ; Nematode Infections/parasitology ; Nematode Infections/veterinary ; Peromyscus/parasitology ; Peromyscus/physiology ; Population Density ; Reproduction/physiology ; Rodent Diseases/parasitology ; Sciuridae/physiology ; Seasons ; Shrews/physiology ; Survival Analysis ; Time Factors
Chemical Substances	Dietary Carbohydrates
Language	English
Publishing date	2009-01
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	3024-7
ISSN	1365-2656 ; 0021-8790
ISSN (online)	1365-2656
ISSN	0021-8790
DOI	10.1111/j.1365-2656.2008.01456.x
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Article ; Online: A CNN model for predicting binding affinity changes between SARS-CoV-2 spike RBD variants and ACE2 homologues

Chen, Chen / Boorla, Veda Sheeresh / Chowdhury, Ratul / Nissly, Ruth H / Gontu, Abhinay / Chothe, Shubhada K / LaBella, Lindsey / Jakka, Padmaja / Ramasamy, Santhamani / Vandegrift, Kurt J / Surendran Nair, Meera / Kuchipudi, Suresh V / Maranas, Costas D

bioRxiv

Abstract	The cellular entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) involves the association of its receptor binding domain (RBD) with human angiotensin converting enzyme 2 (hACE2) as the first crucial step. Efficient and reliable prediction of RBD-hACE2 binding affinity changes upon amino acid substitutions can be valuable for public health surveillance and monitoring potential spillover and adaptation into non-human species. Here, we introduce a convolutional neural network (CNN) model trained on protein sequence and structural features to predict experimental RBD-hACE2 binding affinities of 8,440 variants upon single and multiple amino acid substitutions in the RBD or ACE2. The model achieves a classification accuracy of 83.28% and a Pearson correlation coefficient of 0.85 between predicted and experimentally calculated binding affinities in five-fold cross-validation tests and predicts improved binding affinity for most circulating variants. We pro-actively used the CNN model to exhaustively screen for novel RBD variants with combinations of up to four single amino acid substitutions and suggested candidates with the highest improvements in RBD-ACE2 binding affinity for human and animal ACE2 receptors. We found that the binding affinity of RBD variants against animal ACE2s follows similar trends as those against human ACE2. White-tailed deer ACE2 binds to RBD almost as tightly as human ACE2 while cattle, pig, and chicken ACE2s bind weakly. The model allows testing whether adaptation of the virus for increased binding with other animals would cause concomitant increases in binding with hACE2 or decreased fitness due to adaptation to other hosts.
Keywords	covid19
Language	English
Publishing date	2022-03-23
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2022.03.22.485413
Database	COVID19

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Article ; Online: An ecological and conservation perspective on advances in the applied virology of zoonoses.

Vandegrift, Kurt J / Wale, Nina / Epstein, Jonathan H

Viruses

2011 Volume 3, Issue 4, Page(s) 379–397

Abstract: The aim of this manuscript is to describe how modern advances in our knowledge of viruses and viral evolution can be applied to the fields of disease ecology and conservation. We review recent progress in virology and provide examples of how it is ... ...

Abstract	The aim of this manuscript is to describe how modern advances in our knowledge of viruses and viral evolution can be applied to the fields of disease ecology and conservation. We review recent progress in virology and provide examples of how it is informing both empirical research in field ecology and applied conservation. We include a discussion of needed breakthroughs and ways to bridge communication gaps between the field and the lab. In an effort to foster this interdisciplinary effort, we have also included a table that lists the definitions of key terms. The importance of understanding the dynamics of zoonotic pathogens in their reservoir hosts is emphasized as a tool to both assess risk factors for spillover and to test hypotheses related to treatment and/or intervention strategies. In conclusion, we highlight the need for smart surveillance, viral discovery efforts and predictive modeling. A shift towards a predictive approach is necessary in today's globalized society because, as the 2009 H1N1 pandemic demonstrated, identification post-emergence is often too late to prevent global spread. Integrating molecular virology and ecological techniques will allow for earlier recognition of potentially dangerous pathogens, ideally before they jump from wildlife reservoirs into human or livestock populations and cause serious public health or conservation issues.
MeSH term(s)	Animals ; Communicable Diseases, Emerging/epidemiology ; Communicable Diseases, Emerging/transmission ; Communicable Diseases, Emerging/virology ; Disease Reservoirs/veterinary ; Disease Reservoirs/virology ; Global Health ; Humans ; Virology ; Virus Physiological Phenomena ; Viruses/classification ; Viruses/genetics ; Viruses/isolation & purification ; Zoonoses/epidemiology ; Zoonoses/transmission ; Zoonoses/virology
Keywords	covid19
Language	English
Publishing date	2011-04-15
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v3040379
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