Publications by authors named "Randall W Renshaw"

19 Publications

  • Page 1 of 1

Susceptibility of white-tailed deer () to SARS-CoV-2.

J Virol 2021 Mar 10. Epub 2021 Mar 10.

Department of Population Medicine and Diagnostic Sciences, Animal Health Diagnostic Center, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA

The origin of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing the global coronavirus disease 19 (COVID-19) pandemic, remains a mystery. Current evidence suggests a likely spillover into humans from an animal reservoir. Understanding the host range and identifying animal species that are susceptible to SARS-CoV-2 infection may help to elucidate the origin of the virus and the mechanisms underlying cross-species transmission to humans. Here we demonstrated that white-tailed deer (), an animal species in which the angiotensin converting enzyme 2 (ACE2) - the SARS-CoV-2 receptor - shares a high degree of similarity to humans, are highly susceptible to infection. Intranasal inoculation of deer fawns with SARS-CoV-2 resulted in established subclinical viral infection and shedding of infectious virus in nasal secretions. Notably, infected animals transmitted the virus to non-inoculated contact deer. Viral RNA was detected in multiple tissues 21 days post-inoculation (pi). All inoculated and indirect contact animals seroconverted and developed neutralizing antibodies as early as day 7 pi. The work provides important insights into the animal host range of SARS-CoV-2 and identifies white-tailed deer as a susceptible wild animal species to the virus.Given the presumed zoonotic origin of SARS-CoV-2, the human-animal-environment interface of COVID-19 pandemic is an area of great scientific and public- and animal-health interest. Identification of animal species that are susceptible to infection by SARS-CoV-2 may help to elucidate the potential origin of the virus, identify potential reservoirs or intermediate hosts, and define the mechanisms underlying cross-species transmission to humans. Additionally, it may also provide information and help to prevent potential reverse zoonosis that could lead to the establishment of a new wildlife hosts. Our data show that upon intranasal inoculation, white-tailed deer became subclinically infected and shed infectious SARS-CoV-2 in nasal secretions and feces. Importantly, indirect contact animals were infected and shed infectious virus, indicating efficient SARS-CoV-2 transmission from inoculated animals. These findings support the inclusion of wild cervid species in investigations conducted to assess potential reservoirs or sources of SARS-CoV-2 of infection.
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http://dx.doi.org/10.1128/JVI.00083-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139686PMC
March 2021

Active surveillance of pathogens from ticks collected in New York State suburban parks and schoolyards.

Zoonoses Public Health 2020 09 22;67(6):684-696. Epub 2020 Jul 22.

Department of Population Medicine and Diagnostic Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY, USA.

Schoolyards and suburban parks are two environments where active tick surveillance may inform local management approaches. Even in a state such as New York with a robust active tick surveillance programme operated by the state Department of Health, these settings are not routinely covered. The goal of this study was to highlight the importance of active surveillance for tick-borne pathogens by describing their prevalence in ticks collected from schoolyards and suburban parks and to guide the use of integrated pest management in these settings. Tick dragging was performed in three regions of New York State: Long Island, the Lower Hudson Valley and the Capital Region. A total of 19 schoolyards and 32 parks were sampled. The location, habitat and weather at the time of tick collection were recorded. Ticks were speciated and tested for the presence of 17 pathogens with a novel application of nanoscale real-time PCR. The causative agents of Lyme disease, anaplasmosis, babesiosis and Powassan virus disease were all detected from Ixodes scapularis in various sites throughout the capital region and south-eastern counties of New York state. The most common agent detected was Borrelia burgdorferi, and coinfection rates were as high as 36%. This surveillance study also captured the first of the invasive Asian longhorned tick species, Haemaphysalis longicornis, in New York state (collected 2 June 2017). Results from this study highlight the importance of collaborative efforts and data sharing for improvement of surveillance for tick-borne disease agents.
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http://dx.doi.org/10.1111/zph.12749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496946PMC
September 2020

Equine pegiviruses cause persistent infection of bone marrow and are not associated with hepatitis.

PLoS Pathog 2020 07 10;16(7):e1008677. Epub 2020 Jul 10.

Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Hvidovre Hospital and Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.

Pegiviruses frequently cause persistent infection (as defined by >6 months), but unlike most other Flaviviridae members, no apparent clinical disease. Human pegivirus (HPgV, previously GBV-C) is detectable in 1-4% of healthy individuals and another 5-13% are seropositive. Some evidence for infection of bone marrow and spleen exists. Equine pegivirus 1 (EPgV-1) is not linked to disease, whereas another pegivirus, Theiler's disease-associated virus (TDAV), was identified in an outbreak of acute serum hepatitis (Theiler's disease) in horses. Although no subsequent reports link TDAV to disease, any association with hepatitis has not been formally examined. Here, we characterized EPgV-1 and TDAV tropism, sequence diversity, persistence and association with liver disease in horses. Among more than 20 tissue types, we consistently detected high viral loads only in serum, bone marrow and spleen, and viral RNA replication was consistently identified in bone marrow. PBMCs and lymph nodes, but not liver, were sporadically positive. To exclude potential effects of co-infecting agents in experimental infections, we constructed full-length consensus cDNA clones; this was enabled by determination of the complete viral genomes, including a novel TDAV 3' terminus. Clone derived RNA transcripts were used for direct intrasplenic inoculation of healthy horses. This led to productive infection detectable from week 2-3 and persisting beyond the 28 weeks of study. We did not observe any clinical signs of illness or elevation of circulating liver enzymes. The polyprotein consensus sequences did not change, suggesting that both clones were fully functional. To our knowledge, this is the first successful extrahepatic viral RNA launch and the first robust reverse genetics system for a pegivirus. In conclusion, equine pegiviruses are bone marrow tropic, cause persistent infection in horses, and are not associated with hepatitis. Based on these findings, it may be appropriate to rename the group of TDAV and related viruses as EPgV-2.
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http://dx.doi.org/10.1371/journal.ppat.1008677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375656PMC
July 2020

First report of equine parvovirus-hepatitis-associated Theiler's disease in Europe.

Equine Vet J 2020 Nov 25;52(6):841-847. Epub 2020 Mar 25.

Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.

Background: Equine parvovirus-hepatitis (EqPV-H) has been proposed as the aetiological cause of Theiler's disease, also known as serum hepatitis. EqPV-H-associated Theiler's disease has not been previously reported in Europe.

Objectives: To determine whether EqPV-H infection was associated with a 2018-2019 outbreak of Theiler's disease in four horses on a studfarm.

Study Design: Descriptive case series.

Methods: The medical records of four horses from the same farm diagnosed with fatal Theiler's disease were examined retrospectively. Information collected included a clinical history, physical examination findings, tetanus antitoxin exposure, serum biochemistry and necropsy reports. Liver tissue from all four horses was tested for EqPV-H using PCR and in situ hybridisation (ISH) assays.

Results: Three of the horses had a history of recent (7-11 weeks) tetanus antitoxin administration. Liver tissue from all four horses tested positive for EqPV-H with PCR. In situ hybridisation revealed a widespread distribution of viral nucleic acid in hepatocytes in one case, and a more sporadic distribution in the remaining three cases.

Main Limitations: Case controls were not available from the farm in question given the retrospective nature of analysis.

Conclusions: This case series documents the first reported EqPV-H-associated Theiler's disease in Europe and the first use of ISH to visualise the viral nucleic acid in liver tissues of horses with Theiler's disease.
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http://dx.doi.org/10.1111/evj.13254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483838PMC
November 2020

A NOVEL ORTHOREOVIRUS ASSOCIATED WITH EPIZOOTIC NECROTIZING ENTERITIS AND SPLENIC NECROSIS IN AMERICAN CROWS ().

J Wildl Dis 2019 10 20;55(4):812-822. Epub 2019 May 20.

Department of Population Medicine and Diagnostic Sciences, Animal Health Diagnostic Center, Cornell School of Veterinary Medicine, 240 Farrier Road, Ithaca, New York 14853, USA.

Epizootic mortalities in American Crows () during the winter months, referred to as winter mortality of crows, have been recorded in North America for almost two decades. The most common postmortem findings include necrotizing enteritis, colitis, and fibrinous splenic necrosis. These findings are proposed to be due to infection with a sp. Our objectives were to characterize the pathology and seasonality of the epizootics in New York State (NYS), confirm the causative role of an sp., and determine its phylogeny. On the basis of our proposed case definition for reovirosis, we examined case data collected by the NYS Wildlife Health Program for 16 yr. A total of 558 cases of reovirosis were recorded between 2001 and 2017. Reovirosis had a clear seasonal presentation: cases occurred almost exclusively in winter months (71% in December-January). Detailed data from a 2-yr period (2016-17) demonstrated that reovirosis caused up to 70% of all recorded crow deaths during epizootic months. Crows with positive orthoreovirus isolation from the spleen or intestine were 32 times more likely to die with characteristic histologic lesions of enteritis or enterocolitis and splenic necrosis than crows with negative isolation results. An in situ hybridization probe specific to virus isolated from NYS crow reovirosis cases demonstrated a direct association between viral presence and characteristic histologic lesions. Sigma C (capsid protein) sequences of isolates from NYS crows showed high homology with Tvärminne avian virus, recently proposed as a novel clade, and only distantly related to the avian orthoreovirus clade. Our study indicated that a novel orthoreovirus was the cause of winter mortality (or reovirosis) of American Crows and placed the NYS isolates in the newly proposed genus of .
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October 2019

Viral testing of 18 consecutive cases of equine serum hepatitis: A prospective study (2014-2018).

J Vet Intern Med 2019 Jan 5;33(1):251-257. Epub 2018 Dec 5.

Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York.

Background: Three flaviviruses (equine pegivirus [EPgV]; Theiler's disease-associated virus [TDAV]; non-primate hepacivirus [NPHV]) and equine parvovirus (EqPV-H) are present in equine blood products; the TDAV, NPHV, and EqPV-H have been suggested as potential causes of serum hepatitis.

Objective: To determine the prevalence of these viruses in horses with equine serum hepatitis.

Animals: Eighteen horses diagnosed with serum hepatitis, enrolled from US referral hospitals.

Methods: In the prospective case study, liver, serum, or both samples were tested for EPgV, TDAV, NPHV, and EqPV-H by PCR.

Results: Both liver tissue and serum were tested for 6 cases, serum only for 8 cases, and liver only for 4 cases. Twelve horses received tetanus antitoxin (TAT) 4-12.7 weeks (median = 8 weeks), 3 horses received commercial equine plasma 6-8.6 weeks, and 3 horses received allogenic stem cells 6.4-7.6 weeks before the onset of hepatic failure. All samples were TDAV negative. Two of 14 serum samples were NPHV-positive. Six of 14 serum samples were EPgV-positive. All liver samples were NPHV-negative and EPgV-negative. EqPV-H was detected in the serum (N = 8), liver (N = 4), or both samples (N = 6) of all 18 cases. The TAT of the same lot number was available for virologic testing in 10 of 12 TAT-associated cases, and all 10 samples were EqPV-H positive.

Conclusions And Clinical Importance: We demonstrated EqPV-H in 18 consecutive cases of serum hepatitis. EPgV, TDAV, and NPHV were not consistently present. This information should encourage blood product manufacturers to test for EqPV-H and eliminate EqPV-H-infected horses from their donor herds.
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http://dx.doi.org/10.1111/jvim.15368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335536PMC
January 2019

Viral testing of 10 cases of Theiler's disease and 37 in-contact horses in the absence of equine biologic product administration: A prospective study (2014-2018).

J Vet Intern Med 2019 Jan 6;33(1):258-265. Epub 2018 Dec 6.

Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York.

Background: A novel equine parvovirus (EqPV-H) was recently discovered in the equine liver with Theiler's disease.

Objectives: To determine the prevalence of EqPV-H infection in naturally occurring Theiler's disease cases and in-contact horses in the absence of historical equine biologic product administration.

Animals: Ten cases of Theiler's disease from 6 separate properties were included in the study, based on the criteria of acute onset of clinical signs of liver failure with laboratory or histopathologic findings characteristic of Theiler's disease and no history of receiving an equine biologic product within the preceding 4 months. In addition, 37 in-contact horses from 4 of the 6 properties were screened for EqPV-H infection and hepatitis.

Methods: In prospective case series, cases were diagnosed with Theiler's disease by the attending veterinarian and were tested for EqPV-H by PCR of liver or serum. In-contact horses were assessed via serum chemistry and PCR at the attending veterinarian's discretion. Hepatitis was defined as serum gamma-glutamyltransferase activity above reference interval. The association of EqPV-H with hepatitis was determined by Fisher's exact test.

Results: Nine of 10 (90%) Theiler's disease cases and 54% of tested in-contact horses were EqPV-H positive. Hepatitis was significantly associated with EqPV-H infection (P = .036).

Conclusions And Clinical Importance: Although further study is required to identify EqPV-H as the causative agent of Theiler's disease, EqPV-H appears strongly associated with cases of fatal Theiler's disease and subclinical hepatitis in horses in contact with those cases. The prevalence of EqPV-H infection on affected properties can be high.
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http://dx.doi.org/10.1111/jvim.15362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335540PMC
January 2019

Characterization of a Vesivirus Associated with an Outbreak of Acute Hemorrhagic Gastroenteritis in Domestic Dogs.

J Clin Microbiol 2018 05 25;56(5). Epub 2018 Apr 25.

Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA

Four of eleven affected dogs died despite aggressive treatment during a 2015 focal outbreak of hemorrhagic gastroenteritis following a stay in a pet housing facility. Routine diagnostic investigations failed to identify a specific cause. Virus isolation from fresh necropsy tissues yielded a calicivirus with sequence homology to a vesivirus within the group colloquially known as the vesivirus 2117 strains that were originally identified as contaminants in CHO cell bioreactors. hybridization and reverse transcription-PCR assays of tissues from the four deceased dogs confirmed the presence of canine vesivirus (CaVV) nucleic acids that localized to endothelial cells of arterial and capillary blood vessels. CaVV nucleic acid corresponded to areas of necrosis and hemorrhage primarily in the intestinal tract, but also in the brain of one dog with nonsuppurative meningoencephalitis. This is the first report of an atypical disease association with a putative hypervirulent vesivirus strain in dogs, as all other known strains of CaVV appear to cause nonclinical infections or relatively mild disease. After identification of the CU-296 vesivirus strain from this outbreak, four additional CaVV strains were amplified from unrelated fecal specimens and archived stocks provided by other laboratories. Broader questions include the origins, reservoir(s), and potential for reemergence and spread of these related CaVVs.
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http://dx.doi.org/10.1128/JCM.01951-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5925730PMC
May 2018

New Parvovirus Associated with Serum Hepatitis in Horses after Inoculation of Common Biological Product.

Emerg Infect Dis 2018 02;24(2):303-310

Equine serum hepatitis (i.e., Theiler's disease) is a serious and often life-threatening disease of unknown etiology that affects horses. A horse in Nebraska, USA, with serum hepatitis died 65 days after treatment with equine-origin tetanus antitoxin. We identified an unknown parvovirus in serum and liver of the dead horse and in the administered antitoxin. The equine parvovirus-hepatitis (EqPV-H) shares <50% protein identity with its phylogenetic relatives of the genus Copiparvovirus. Next, we experimentally infected 2 horses using a tetanus antitoxin contaminated with EqPV-H. Viremia developed, the horses seroconverted, and acute hepatitis developed that was confirmed by clinical, biochemical, and histopathologic testing. We also determined that EqPV-H is an endemic infection because, in a cohort of 100 clinically normal adult horses, 13 were viremic and 15 were seropositive. We identified a new virus associated with equine serum hepatitis and confirmed its pathogenicity and transmissibility through contaminated biological products.
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http://dx.doi.org/10.3201/eid2402.171031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5782890PMC
February 2018

High-throughput Detection of Respiratory Pathogens in Animal Specimens by Nanoscale PCR.

J Vis Exp 2016 11 28(117). Epub 2016 Nov 28.

Population Medicine and Diagnostic Sciences, Cornell University Animal Health Diagnostic Center.

Nanoliter scale real-time PCR uses spatial multiplexing to allow multiple assays to be run in parallel on a single plate without the typical drawbacks of combining reactions together. We designed and evaluated a panel based on this principle to rapidly identify the presence of common disease agents in dogs and horses with acute respiratory illness. This manuscript describes a nanoscale diagnostic PCR workflow for sample preparation, amplification, and analysis of target pathogen sequences, focusing on procedures that are different from microliter scale reactions. In the respiratory panel presented, 18 assays were each set up in triplicate, accommodating up to 48 samples per plate. A universal extraction and pre-amplification workflow was optimized for high-throughput sample preparation to accommodate multiple matrices and DNA and RNA based pathogens. Representative data are presented for one RNA target (influenza A matrix) and one DNA target (equine herpesvirus 1). The ability to quickly and accurately test for a comprehensive, syndrome-based group of pathogens is a valuable tool for improving efficiency and ergonomics of diagnostic testing and for acute respiratory disease diagnosis and management.
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http://dx.doi.org/10.3791/54781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5226323PMC
November 2016

Characterization of nonprimate hepacivirus and construction of a functional molecular clone.

Proc Natl Acad Sci U S A 2015 Feb 2;112(7):2192-7. Epub 2015 Feb 2.

Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065;

Nonprimate hepacivirus (NPHV) is the closest known relative of hepatitis C virus (HCV) and its study could enrich our understanding of HCV evolution, immunity, and pathogenesis. High seropositivity is found in horses worldwide with ∼ 3% viremic. NPHV natural history and molecular virology remain largely unexplored, however. Here, we show that NPHV, like HCV, can cause persistent infection for over a decade, with high titers and negative strand RNA in the liver. NPHV is a near-universal contaminant of commercial horse sera for cell culture. The complete NPHV 3'-UTR was determined and consists of interspersed homopolymer tracts and an HCV-like 3'-terminal poly(U)-X-tail. NPHV translation is stimulated by miR-122 and the 3'-UTR and, similar to HCV, the NPHV NS3-4A protease can cleave mitochondrial antiviral-signaling protein to inactivate the retinoic acid-inducible gene I pathway. Using an NPHV consensus cDNA clone, replication was not observed in primary equine fetal liver cultures or after electroporation of selectable replicons. However, intrahepatic RNA inoculation of a horse initiated infection, yielding high RNA titers in the serum and liver. Delayed seroconversion, slightly elevated circulating liver enzymes and mild hepatitis was observed, followed by viral clearance. This establishes the molecular components of a functional NPHV genome. Thus, NPHV appears to resemble HCV not only in genome structure but also in its ability to establish chronic infection with delayed seroconversion and hepatitis. This NPHV infectious clone and resulting acute phase sera will facilitate more detailed studies on the natural history, pathogenesis, and immunity of this novel hepacivirus in its natural host.
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http://dx.doi.org/10.1073/pnas.1500265112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4343093PMC
February 2015

Safety and immunogenicity of Ontario Rabies Vaccine Bait (ONRAB) in the first us field trial in raccoons (Procyon lotor).

J Wildl Dis 2014 Jul 7;50(3):582-95. Epub 2014 May 7.

1  US Department of Agriculture, Animal and Plant Health Inspection Service, Wildlife Services, National Rabies Management Program, 59 Chenell Drive, Concord, New Hampshire 03301, USA.

In 2011, we conducted a field trial in rural West Virginia, USA to evaluate the safety and immunogenicity of a live, recombinant human adenovirus (AdRG1.3) rabies virus glycoprotein vaccine (Ontario Rabies Vaccine Bait; ONRAB) in wild raccoons (Procyon lotor) and striped skunks (Mephitis mephitis). We selected ONRAB for evaluation because of its effectiveness in raccoon rabies management in Ontario and Quebec, Canada, and significantly higher antibody prevalence rates in raccoons compared with a recombinant vaccinia-rabies glycoprotein (V-RG) vaccine, Raboral V-RG®, in US-Canada border studies. Raccoon rabies was enzootic and oral rabies vaccination (ORV) had never been used in the study area. We distributed 79,027 ONRAB baits at 75 baits/km(2) mostly by fixed-wing aircraft along parallel flight lines at 750-m intervals. Antibody prevalence was significantly higher at 49.2% (n=262) in raccoons after ONRAB was distributed than the 9.6% (n=395) before ORV. This was the highest antibody prevalence observed in raccoons by US Department of Agriculture Wildlife Services for areas with similar management histories evaluated before and after an initial ORV campaign at 75 baits/km(2) with Raboral V-RG. Tetracycline biomarker (TTCC) was significantly higher among antibody-positive raccoons after ONRAB baiting and was similar among raccoons before ORV had been conducted, an indication of vaccine-induced rabies virus-neutralizing antibody production following consumption of bait containing TTCC. Skunk sample size was inadequate to assess ONRAB effects. Safety and immunogenicity results supported replication of this field trial and led to a recommendation for expanded field trials in 2012 to evaluate safety and immunogenicity of ground-distributed ONRAB at 150 baits/km(2) in residential and commercial habitats in Ohio, USA and aerially distributed ONRAB at 75 baits/km(2) in rural habitats along US-Quebec border.
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http://dx.doi.org/10.7589/2013-08-207DOI Listing
July 2014

Detection of canine pneumovirus in dogs with canine infectious respiratory disease.

J Clin Microbiol 2013 Dec 2;51(12):4112-9. Epub 2013 Oct 2.

Department of Pathology and Pathogen Biology, The Royal Veterinary College, North Mymms, Hatfield, Hertfordshire, United Kingdom.

Canine pneumovirus (CnPnV) was recently identified during a retrospective survey of kenneled dogs in the United States. In this study, archived samples from pet and kenneled dogs in the United Kingdom were screened for CnPnV to explore the relationship between exposure to CnPnV and the development of canine infectious respiratory disease (CIRD). Within the pet dog population, CnPnV-seropositive dogs were detected throughout the United Kingdom and Republic of Ireland, with an overall estimated seroprevalence of 50% (n = 314/625 dogs). In the kennel population, there was a significant increase in seroprevalence, from 26% (n = 56/215 dogs) on the day of entry to 93.5% (n = 201/215 dogs) after 21 days (P <0001). Dogs that were seronegative on entry but seroconverted while in the kennel were 4 times more likely to develop severe respiratory disease than those that did not seroconvert (P < 0.001), and dogs with preexisting antibodies to CnPnV on the day of entry were significantly less likely to develop respiratory disease than immunologically naive dogs (P < 0.001). CnPnV was detected in the tracheal tissues of 29/205 kenneled dogs. Detection was most frequent in dogs with mild to moderate respiratory signs and histopathological changes and in dogs housed for 8 to 14 days, which coincided with a significant increase in the risk of developing respiratory disease compared to the risk of those housed 1 to 7 days (P < 0.001). These findings demonstrate that CnPnV is present in the United Kingdom dog population; there is a strong association between exposure to CnPnV and CIRD in the kennel studied and a potential benefit in vaccinating against CnPnV as part of a wider disease prevention strategy.
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http://dx.doi.org/10.1128/JCM.02312-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3838075PMC
December 2013

Novel pneumoviruses (PnVs): Evolution and inflammatory pathology.

Virology 2013 Sep 10;443(2):257-64. Epub 2013 Jun 10.

Inflammation Immunobiology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1883, USA.

A previous report of a novel pneumovirus (PnV) isolated from the respiratory tract of a dog described its significant homology to the rodent pathogen, pneumonia virus of mice (PVM). The original PnV-Ane4 pathogen replicated in and could be re-isolated in infectious state from mouse lung but elicited minimal mortality compared to PVM strain J3666. Here we assess phylogeny and physiologic responses to 10 new PnV isolates. The G/glycoprotein sequences of all PnVs include elongated amino-termini when compared to the characterized PVMs, and suggest division into groups A and B. While we observed significant differences in cytokine production and neutrophil recruitment to the lungs of BALB/c mice in response to survival doses (50 TCID50 units) of representative group A (114378-10-29-KY-F) and group B (7968-11-OK) PnVs, we observed no evidence for positive selection (dN > dS) among the PnV/PnV, PVM/PnV or PVM/PVM G/glycoprotein or F/fusion protein sequence pairs.
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http://dx.doi.org/10.1016/j.virol.2013.05.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3722285PMC
September 2013

Complete genome sequence of a polyomavirus isolated from horses.

J Virol 2012 Aug;86(16):8903

Animal Health Diagnostic Center, Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.

A polyomavirus was isolated from the eyes of horses, and the sequence was determined. A nearly identical VP1 sequence was amplified from the kidney of another animal. We report the complete genome sequence of the first polyomavirus to be isolated from a horse. Analysis shows it to be most closely related overall to human and nonhuman primate polyomaviruses.
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http://dx.doi.org/10.1128/JVI.01261-12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3421721PMC
August 2012

Canine pneumovirus replicates in mouse lung tissue and elicits inflammatory pathology.

Virology 2011 Jul 20;416(1-2):26-31. Epub 2011 May 20.

Laboratory of Allergic Diseases, NIAID, NIH, Bethesda, MD 20892, USA.

Canine pneumovirus (CnPnV) was recently isolated from the respiratory tracts of shelter dogs and shares sequence similarity with the rodent pathogen, pneumonia virus of mice (PVM). We show here that CnPnV replicates in and can elicit local proinflammatory cytokine production and neutrophil recruitment to lung tissue and the airways. In contrast to PVM J3666 infection, fatal CnPnV infections are observed only in response to high titer intranasal inocula (>67 TCID(50) units). Sera from mice that recover from CnPnV infection contain antibodies that cross-react with PVM antigens; these mice are protected against lethal PVM infection. Given these findings, it will be intriguing to determine the relative role(s) of CnPnV and PVM in eliciting respiratory symptoms in susceptible canine species.
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http://dx.doi.org/10.1016/j.virol.2011.04.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3112256PMC
July 2011

Pneumovirus in dogs with acute respiratory disease.

Emerg Infect Dis 2010 Jun;16(6):993-5

Cornell University, Ithaca, New York 14853, USA.

To determine which respiratory viruses circulate among confined dogs, we analyzed nasal and pharyngeal swab specimens from shelter dogs with acute respiratory disease. An unknown virus was isolated. Monoclonal antibody testing indicated that it was probably a pneumovirus. PCR and sequence analysis indicated that it was closely related to murine pneumovirus.
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http://dx.doi.org/10.3201/eid1606.091778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3086219PMC
June 2010

Antiviral activity of geneticin against dengue virus.

Antiviral Res 2009 Jul 11;83(1):21-7. Epub 2009 Mar 11.

Institute of Hepatitis and Viral Research, Drexel University College of Medicine, Doylestown, PA 18902, USA.

The aminoglycoside, geneticin (G418), was recently shown to have antiviral activity against bovine viral diarrhea virus (BVDV). Since BVDV, dengue virus (DENV) and yellow fever virus (YFV) all belong to the Flaviviridae family, it seemed possible that a common step in their life cycle might be affected by this aminoglycoside. Here it is shown that geneticin prevented the cytopathic effect (CPE) resulting from DENV-2 infection of BHK cells, in a dose-dependent manner with an 50% effective concentration (EC(50)) value of 3+/-0.4microg/ml. Geneticin had no detectable effect on CPE caused by YFV in BHK cells. Geneticin also inhibited DENV-2 viral yield with an EC(50) value of 2+/-0.1microg/ml and an EC(90) value of 20+/-2microg/ml. With a CC(50) value of 165+/-5microg/ml, the selectivity index of anti-DENV activity of geneticin in BHK cells was established to be 66. Furthermore, 25microg/ml of geneticin nearly completely blocked plaque formation induced by DENV-2, but not YFV. In addition, geneticin, inhibited DENV-2 viral RNA replication and viral translation. Gentamicin, kanamycin, and the guanidinylated geneticin showed no anti-DENV activity. Neomycin and paromomycin demonstrated weak antiviral activity at high concentrations. Finally, aminoglycoside-3'-phosphotransferase activity of neomycin-resistant gene abolished antiviral activity of geneticin.
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http://dx.doi.org/10.1016/j.antiviral.2009.02.204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2694137PMC
July 2009

Detection of antibodies to West Nile virus in equine sera using microsphere immunoassay.

J Vet Diagn Invest 2006 Jul;18(4):392-5

Equine Viral Disease Laboratory, Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.

One hundred and ninety-one sera from horses that recently were exposed to West Nile virus (WNV) by either vaccination or natural infection or that were not vaccinated and remained free of infection were used to evaluate fluorescent microsphere immunoassays (MIAs) incorporating recombinant WNV envelope protein (rE) and recombinant nonstructural proteins (rNS1, rNS3, and rNS5) for detection of equine antibodies to WNV. The rE MIA had a diagnostic sensitivity and specificity, respectively, of 99.3% and 97.4% for detection of WNV antibodies in the serum of horses that were recently vaccinated or naturally infected with WNV, as compared to the plaque reduction neutralization test (PRNT). The positive rE MIA results were assumed to be WNV-specific because of the close agreement between this assay and the PRNT and the fact that unvaccinated control horses included in this study were confirmed to be free of exposure to the related St Louis encephalitis virus. The NS protein-based MIA were all less sensitive than either the rE MIA or PRNT (sensitivity 0-48.0), although the rNSI MIA distinguished horses vaccinated with the recombinant WNV vaccine from those that were immunized with the inactivated WNV vaccine (P < 0.0001) or naturally infected with WNV (P < 0.0001). The rE MIA would appear to provide a rapid, convenient, inexpensive, and accurate test for the screening of equine sera for the presence of antibodies to WNV.
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http://dx.doi.org/10.1177/104063870601800413DOI Listing
July 2006
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