Publications by authors named "Roger K Maes"

41 Publications

Safety and Efficacy of Felid Herpesvirus-1 Deletion Mutants in Cats.

Viruses 2021 01 22;13(2). Epub 2021 Jan 22.

Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, 784 Wilson Road, East Lansing, MI 48824, USA.

Felid herpesvirus-1 (FeHV-1) is an important respiratory and ocular pathogen of cats and current vaccines are limited in duration and efficacy because they do not prevent infection, viral nasal shedding and latency. To address these shortcomings, we have constructed FeHV-1 gE-TK- and FeHV-1 PK- deletion mutants (gE-TK- and PK-) using bacterial artificial chromosome (BAC) mutagenesis and shown safety and immunogenicity in vitro. Here, we compare the safety and efficacy of a prime boost FeHV-1 gE-TK- and FeHV-1 PK- vaccination regimen with commercial vaccination in cats. Cats in the vaccination groups were vaccinated at 3-week intervals and all cats were challenge infected 3 weeks after the last vaccination. Evaluations included clinical signs, nasal shedding, virus neutralizing antibodies (VN), cytokine mRNA gene expression, post-mortem histology and detection of latency establishment. Vaccination with gE-TK- and PK- mutants was safe and resulted in significantly reduced clinical disease scores, pathological changes, viral nasal shedding, and viral DNA in the trigeminal ganglia (the site of latency) following infection. Both mutants induced VN antibodies and interferons after immunization. In addition, after challenge infection, we observed a reduction of IL-1β expression, and modulation of TNFα, TGFβ and IL10 expression. In conclusion, this study shows the merits of using FeHV-1 deletion mutants for prevention of FeHV-1 infection in cats.
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http://dx.doi.org/10.3390/v13020163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911815PMC
January 2021

Concurrent Infection of Skunk Adenovirus-1, , and a Regionally Specific Clade of Canine Distemper Virus in One Gray Fox () and Concurrent Listeriosis and Canine Distemper in a Second Gray Fox.

Pathogens 2020 Jul 21;9(7). Epub 2020 Jul 21.

New Hampshire Veterinary Diagnostic Laboratory, University of New Hampshire, Durham, NH 03824, USA.

One free-ranging Gray fox () underwent autopsy following neurologic disease, with findings including morbilliviral inclusions and associated lesions in numerous tissues, adenoviral intranuclear inclusions in bronchial epithelial cells, and septic pleuropneumonia, hepatitis, splenitis, and meningoencephalitis. Molecular diagnostics on fresh lung identified a strain within a distinct clade of canine distemper that is currently unique to wildlife in New England, as well as the emerging multi-host viral pathogen skunk adenovirus-1. Bacterial culture of fresh liver resulted in a pure growth of , with whole genome sequencing indicating that the isolate had a vast array of antimicrobial resistance and virulence-associated genes. One year later, a second fox was euthanized for inappropriate behavior in a residential area, and diagnostic workup revealed canine distemper and septic , with the former closely related to the distemper virus found in the previous fox and the latter divergent from the from the previous fox.
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http://dx.doi.org/10.3390/pathogens9070591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400275PMC
July 2020

Necrotizing Ventriculitis in Fledgling Chimney Swifts () Associated With a Novel Adenovirus, Chimney Swift Adenovirus-1 (CsAdV-1).

Vet Pathol 2019 11 22;56(6):907-914. Epub 2019 Jul 22.

Veterinary Diagnostic Laboratory, Michigan State University, East Lansing MI, USA.

Five chimney swift fledglings died following a progressive loss of appetite and condition while being cared for by an experienced wildlife rehabilitator. All animals had severe necrotizing and heterophilic ventriculitis, with myriad epithelial cells characterized by karyomegaly with intranuclear inclusion bodies. Transmission electron microscopy showed distention of epithelial cell nuclei and chromatin peripheralization by nonenveloped, icosahedral, 75- to 85-nm-diameter virions. Degenerate nested PCR for a highly conserved region of the adenovirus DNA polymerase gene was positive. BLAST analysis of the amplicon sequence indicated the presence of a novel adenovirus, with 74% homology to Antarctic penguin adenoviruses and 72% homology to a bat adenovirus, at low query coverages of only 65% and 63%, respectively. BLAST analysis of the predicted amino acid sequence generated the highest scores for squamate adenoviruses at 100% query coverage. Based on phylogenetic analysis of the partial amino acid sequence of the DNA polymerase, the chimney swift virus was a novel adenovirus most closely related to the genus. Using a probe based on the novel viral sequence, DNA in situ hybridization identified viral nucleic acid in the nucleus. While the tentatively named chimney swift adenovirus-1 (CsAdV-1) is so far classified with the Atadenoviruses, it is relatively divergent from other members of that genus and may represent the first identified member of a new genus of Adenoviruses.
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http://dx.doi.org/10.1177/0300985819861717DOI Listing
November 2019

Malignant transformation of canine oral papillomavirus (CPV1)-associated papillomas in dogs: An emerging concern?

Papillomavirus Res 2018 12 9;6:83-89. Epub 2018 Nov 9.

Veterinary Diagnostic Laboratory, College of Veterinary Medicine, Michigan State University, Lansing, Michigan, USA; Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA. Electronic address:

Canine oral papillomavirus (CPV1, also known as COPV), the most common cause of non-neoplastic papillomas, has not been shown to cause squamous cell carcinomas (SCC). Furthermore, malignant transformation of benign papillomas to SCC has only been reported in a single group of dogs with severe combined immunodeficiency infected with CPV2. Here, we report a series of 7 dogs with benign CPV1-associated papillomas with histologic evidence of CPV1 causing malignant transformation to carcinoma in situ and ultimately SCC. Expression of p53 and p16 proteins in CPV1-infected cells within the benign papillomas and lesions that progressed into SCC also supported an association between papillomavirus and malignant transformation. Moreover, our retrospective analysis indicated that while there have been increased numbers of viral papillomas with malignant transformation, the number of annually diagnosed canine viral papillomas has remained constant over the past decade in our laboratory. We speculate that either an altered host immunity from increased usage of immunosuppressive drugs or changing environmental factors, e.g. increase exposure to UV radiation, may cause an increased oncogenic potential of this "low-risk" virus. This study aims to raise awareness of the malignant potential of CPV1 and to encourage further investigations into the cause of this suspected change in its oncogenic potential.
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http://dx.doi.org/10.1016/j.pvr.2018.10.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260289PMC
December 2018

Identification of gammaherpesvirus infection in free-ranging black bears (Ursus americanus).

Virus Res 2019 01 30;259:46-53. Epub 2018 Oct 30.

Department of Biomedical Sciences, Carlson College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331, United States; Department of Microbiology, College of Science, Oregon State University, Corvallis, OR 97331, United States. Electronic address:

Herpesvirus infection was investigated in black bears (Ursus americanus) with neurological signs and brain lesions of nonsuppurative encephalitis of unknown cause. Visible cytopathic effects (CPE) could only be observed on days 3-5 post-infection in HrT-18G cell line inoculated with bear tissue extracts. The observed CPE in HrT-18G cells included syncytia, intranuclear inclusions, and cell detachments seen in herpesvirus infection in vitro. Herpesvirus-like particles were observed in viral culture supernatant under the electron microscope, however, capsids ranging from 60 nm to 100 nm in size were often observed in viral cultures within the first two passages of propagation. Herpesvirus infection in the bear tissues and tissue cultures were detected by PCR using degenerate primers specific to the DNA polymerase gene (DPOL) and glycoprotein B gene (gB). DNA sequencing of the amplicon revealed that the detected herpesvirus has 94-95% identity to Ursid gammaherpesvirus 1 (UrHV-1) DNA sequences of DPOL. Phylogenetic analysis of DPOL sequences indicates that black bear herpesviruses and UrHV-1 are closely related and have small distances to members of Rhadinovirus. Interestingly, black bear herpesvirus infections were also found in bears without neurological signs. The DPOL DNA sequence of black bear herpesviruses detected in neurological bears were similar to the those detected in the non-neurological bears. However, the gB DNA sequence detected from the neurological bear is different from non-neurological bear and has only 64.5%-70% identity to each other. It is possible that at least two different types of gammaherpesviruses are present in the U. americanus population or several gammaherpesviruses exist in ursine species.
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http://dx.doi.org/10.1016/j.virusres.2018.10.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114836PMC
January 2019

Genomic characterization of Erethizon dorsatum papillomavirus 2, a new papillomavirus species marked by its exceptional genome size.

J Gen Virol 2018 12 24;99(12):1699-1704. Epub 2018 Oct 24.

1​KU Leuven, Department of Microbiology and Immunology, Laboratory of Clinical Virology, Rega Institute for Medical Research, Herestraat 49/Box 1040, BE3000 Leuven, Belgium.

We report here the complete sequence and genome organization of a new papillomavirus, Erethizon dorsatum papillomavirus 2 (EdPV2), which was isolated from cutaneous lesions observed on the muzzle of a North American porcupine. The complete genome is 8809 nucleotides long and encodes five early (E6-E7-E1-E2-E4) and two late proteins (L2-L1). In addition to the upstream regulatory region, the EdPV2 genome contains an exceptionally large secondary non-coding region with no apparent functional relevance. EdPV2 is strongly divergent from the previously described porcupine papillomavirus EdPV1 and phylogenetic analysis shows EdPV2 clustering near members of the genus Pipapillomavirus, a group of rodent papillomaviruses. Pairwise sequence comparison based on the L1 open reading frame identifies Rattus norvegicus papillomavirus 1 as the closest related virus (59.97 % similarity). Based on its low sequence similarity to other known papillomaviruses, EdPV2 is thought to represent a new genus in the family Papillomaviridae.
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http://dx.doi.org/10.1099/jgv.0.001164DOI Listing
December 2018

Abortigenic but Not Neurotropic Equine Herpes Virus 1 Modulates the Interferon Antiviral Defense.

Front Cell Infect Microbiol 2018 12;8:312. Epub 2018 Sep 12.

Department of Virology, Immunology and Parasitology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.

Equine herpesvirus 1 (EHV1) is considered as a major pathogen of , causing symptoms from mild respiratory disease to late-term abortion and neurological disorders. Different EHV1 strains circulating in the field have been characterized to be of abortigenic or neurovirulent phenotype. Both variants replicate in a plaque-wise manner in the epithelium of the upper respiratory tract (URT), where the abortigenic strains induce more prominent viral plaques, compared to the neurovirulent strains. Considering the differences in replication at the URT, we hypothesized that abortigenic strains may show an increased ability to modulate the type I IFN secretion/signaling pathway, compared to strains that display the neurovirulent phenotype. Here, we analyze IFN levels induced by abortigenic and neurovirulent EHV1 using primary respiratory epithelial cells (EREC) and respiratory mucosa explants. Similar levels of IFNα (~70 U/ml) were detected in explants inoculated with both types of EHV1 strains from 48 to 72 hpi. Second, EREC and mucosa explants were treated with recombinant equine IFNα (rEqIFNα) or Ruxolitinib (Rux), an IFN signaling inhibitor, prior to and during inoculation with abortigenic or neurovirulent EHV1. Replication of both EHV1 variants was suppressed by rEqIFNα. Further, addition of Rux increased replication in a concentration-dependent manner, indicating an IFN-susceptibility for both variants. However, in two out of three horses, at a physiological concentration of 100 U/ml of rEqIFNα, an increase in abortigenic EHV1 replication was observed compared to 10 U/ml of rEqIFNα, which was not observed for the neurovirulent strains. Moreover, in the presence of Rux, the plaque size of the abortigenic variants remained unaltered, whereas the typically smaller viral plaques induced by the neurovirulent variants became larger. Overall, our results demonstrate the importance of IFNα in the control of EHV1 replication in the URT for both abortigenic and neurovirulent variants. In addition, our findings support the speculation that abortigenic variants of EHV1 may have developed anti-IFN mechanisms that appear to be absent or less pronounced in neurovirulent EHV1 strains.
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http://dx.doi.org/10.3389/fcimb.2018.00312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6144955PMC
August 2019

Zebra-borne neurotropic equid herpesvirus 1 meningoencephalitis in a Thomson's gazelle ( Eudorcas thomsonii).

J Vet Diagn Invest 2017 Jul 20;29(4):548-556. Epub 2017 Apr 20.

Louisiana State University, Department of Pathobiology, Baton Rouge, LA (Sakaguchi, Kim, Langohr, Gaschen, Del Piero).

We describe the histopathologic, immunohistochemical, and molecular features of a case of meningoencephalitis in a Thomson's gazelle ( Eudorcas thomsonii) naturally infected with zebra-borne equid herpesvirus 1 (EHV-1) and the implications for the molecular detection of zebra-borne EHV-1. A 4-y-old female Thomson's gazelle was submitted for postmortem examination; no gross abnormalities were noted except for meningeal congestion. Microscopic evaluation demonstrated multifocal nonsuppurative meningoencephalitis with intranuclear eosinophilic and amphophilic inclusion bodies and EHV-9 antigen in neurons. PCR demonstrated the presence of a herpesvirus with a nucleotide sequence 99-100% identical to the corresponding sequences of zebra-borne EHV-1 and of EHV-9 strains. To determine whether EHV-1 or EHV-9 was involved, a PCR with a specific primer set for EHV-9 ORF59/60 was used. The sequence was identical to that of 3 recognized zebra-borne EHV-1 strains and 91% similar to that of EHV-9. This isolate was designated as strain LM2014. The partial glycoprotein G ( gG) gene sequence of LM2014 was also identical to the sequence of 2 zebra-borne EHV-1 strains (T-529 isolated from an onager, 94-137 from a Thomson's gazelle). The histologic lesions of encephalitis and antigen localization in this gazelle indicate prominent viral neurotropism, and lesions were very similar to those seen in EHV-1- and EHV-9-infected non-equid species. Histologic lesions caused by EHV-9 and zebra-borne EHV-1 are therefore indistinguishable.
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http://dx.doi.org/10.1177/1040638717707000DOI Listing
July 2017

Reduced humoral immunity and atypical cell-mediated immunity in response to vaccination in cows naturally infected with bovine leukemia virus.

Vet Immunol Immunopathol 2016 Dec 23;182:125-135. Epub 2016 Oct 23.

Department of Animal Science, Michigan State University, 474 S. Shaw Lane, East Lansing, MI 48824, United States.

Bovine leukemia virus (BLV) is a retrovirus that is widely distributed across US dairy herds: over 83% of herds are BLV-infected and within-herd infection rates can approach 50%. BLV infection reduces both animal longevity and milk production and can interfere with normal immune health. With such a high prevalence of BLV infection in dairy herds, it is essential to understand the circumstances by which BLV negatively affects the immune system of infected cattle. To address this question, BLV- and BLV+ adult, lactating Holstein dairy cows were vaccinated with Bovi-Shield GOLD FP 5 L5 HB and their immune response to vaccination was measured over the course of 28days. On day 0 prior to vaccination and days 7, 14 and 28 post-vaccination, fresh PBMCs were characterized for T and B cell ratios in the periphery. Plasma was collected to measure titers of IgM, IgG1 and IgG2 produced against bovine herpesvirus 1 (BHV1), Leptospira hardjo and L. pomona, as well as to characterize neutralizing antibody titers produced against BHV1 and bovine viral diarrhea virus types 1 and 2. On day 18 post-vaccination, PBMCs were cultured in the presence of BHV1 and flow cytometry was used to determine IFNγ production by CD4+, CD8+ and γδ T cells and to investigate CD25 and MHCII expression on B cells. BLV+ cows produced significantly lower titers of IgM against BHV1, L. hardjo and L. pomona and produced lower titers of IgG2 against BHV1. γδ T cells from BLV+ cows displayed a hyper reactive response to stimulation in vitro, although no differences were observed in CD4+ or CD8+ T cell activation. Finally, B cells from BLV+ cows exhibited higher CD25 expression and reduced MHCII expression in response to stimulation in vitro. All together, data from this study support the hypothesis that BLV+ cows fail to respond to vaccination as strongly as BLV- cows and, consequently, may have reduced protective immunity when compared to healthy BLV- cows.
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http://dx.doi.org/10.1016/j.vetimm.2016.10.013DOI Listing
December 2016

In vitro characterization of felid herpesvirus 1 (FHV-1) mutants generated by recombineering in a recombinant BAC vector.

Virus Res 2016 08 6;221:15-22. Epub 2016 May 6.

Graduate Program in Comparative Medicine and Integrative Biology, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA; Diagnostic Center for Population and Animal Health, College of Veterinary Medicine, Michigan State University, 4125 Beaumont Road, Lansing, MI 48910, USA; Department of Microbiology and Molecular Genetics, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA; Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA. Electronic address:

Felid herpesvirus 1 (FHV-1) mutants were constructed using two-step Red-mediated recombination techniques based on a virulent full-length FHV-1 BAC clone. The individual mutant viruses generated were deficient in glycoprotein C (gC), glycoprotein E (gE), US3 serine/threonine protein kinase (PK), or both gE and thymidine kinase (TK). The gC- mutant virus produced plaques that were similar in size to those resulting from infection with the C-27 parent strain. In contrast, the gE(-), PK(-), and gE(-)PK(-) deletion mutants produced plaques that were significantly smaller. Multistep in vitro growth kinetics of the gE(-), PK(-), and gE(-)PK(-) viruses were slightly delayed compared to those of the C-27 parent strain. Peak progeny titers of these three mutants were approximately 10-fold lower than those generated with the C-27 strain. There was no delay in the growth kinetics of the gC- mutant, but the progeny virus titer obtained with this mutant was at least 3 logs lower compared to the parental strain titer. Based upon their in vitro characteristics, these mutants will be useful for the development of novel immunization strategies against this important feline pathogen.
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http://dx.doi.org/10.1016/j.virusres.2016.05.001DOI Listing
August 2016

Herpes simplex encephalitis in a captive black howler monkey (Alouatta caraya).

J Vet Diagn Invest 2016 Jan 23;28(1):76-8. Epub 2015 Dec 23.

Diagnostic Center for Population and Animal Health (Barnes, Wise, Maes, Kiupel), Michigan State University, Lansing, MIDepartment of Pathobiology and Diagnostic Investigation (Maes, Kiupel), Michigan State University, Lansing, MINorthwest ZooPath, Monroe, WA (Garner)California Animal Health and Food Safety, University of California-Davis, Davis, CA (Persiani).

An 18-month-old captive black howler monkey (Alouatta caraya) died after a 3-day history of neurologic signs. Gross findings at autopsy were limited to bloody, yellow, and foul-smelling intestinal contents. Histologically, there was extensive necrotizing meningoencephalitis predominantly in both cerebral hemispheres, and lymphohistiocytic, neutrophilic infiltrate expanded the subarachnoid and Virchow-Robbin space. In the most severely affected regions, neurons contained eosinophilic intranuclear inclusion bodies surrounded by a clear halo and margination of the chromatin. Electron microscopy of the affected cells revealed numerous intranuclear viral particles characteristic of herpesvirus. Immunohistochemically, neurons and glial cells in the affected regions were labeled with a monoclonal antibody against Human herpesvirus 1, and was confirmed by polymerase chain reaction.
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http://dx.doi.org/10.1177/1040638715613379DOI Listing
January 2016

Evaluation of Trapper-Collected Nobuto Filter-Paper Blood Samples for Distemper and Parvovirus Antibody Detection in Coyotes (Canis latrans) and Raccoons (Procyon lotor).

J Wildl Dis 2015 Jul 14;51(3):724-8. Epub 2015 May 14.

4  Diagnostic Center for Population and Animal Health, Michigan State University, 4125 Beaumont Road, Lansing, Michigan 48910, USA.

Blood samples are often collected from free-ranging wildlife for antibody detection. However, filter-paper (FP) strips are more cost efficient and easy to collect and store. We evaluated trapper-collected FP strips and body-cavity blood for canine distemper (CDV) and parvovirus (CPV-2) antibody detection in raccoons (Procyon lotor) and coyotes (Canis latrans). From 2008 to 2010, licensed trappers near Madison and Milwaukee, Wisconsin, US collected paired samples from harvested animals. Canine distemper antibodies were detected using virus neutralization and parvovirus antibodies were detected using hemagglutination inhibition. Titers ≥ 1:32 for CDV and ≥ 1:25 for CPV-2 were considered evidence of exposure. Using Cohen's kappa test of agreement, FP strip titers agreed with sera for CDV in coyotes (n = 28, K = 0.772) and raccoons (n = 29, K = 0.858) and for CPV-2 in coyotes (n = 40, K = 0.775) and raccoons (n = 70, K = 0.646). However, raccoons determined to be exposed to CPV-2 from sera were unexposed by FP strips in 35% of the samples. Titer results may be affected by quality and volume of blood samples, interval between collection and processing, small sample sizes, and diagnostic testing procedures. Filter-paper strips can be useful for detecting CDV and CPV-2 exposure in coyotes and raccoons with correct field sample collection and appropriate diagnostic testing procedures.
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http://dx.doi.org/10.7589/2014-06-147DOI Listing
July 2015

Two Cases of Systemic Coronavirus-Associated Disease Resembling Feline Infectious Peritonitis in Domestic Ferrets in Japan.

J Exot Pet Med 2014 Apr 3;23(2):196-200. Epub 2014 Mar 3.

Miyazaki University Veterinary Teaching Hospital, Miyazaki-city, Japan.

A systemic disease of domestic ferrets characterized by pyogranulomatous inflammation was first recognized in Europe and the United States in 2002. The disease closely resembled feline infectious peritonitis and subsequently has been shown to be associated with ferret systemic coronavirus (FRSCV). A definitive laboratory diagnosis of this disease is typically based on a combination of immunohistochemistry (IHC) and reverse-transcriptase polymerase chain reaction tests to detect FRSCV in granulomatous lesions. In 2010, this feline infectious peritonitis-like disease was first identified in a laboratory ferret in Japan, and laboratory confirmation of the clinical diagnosis was limited to IHC. This report describes 2 cases of systemic coronavirus-associated disease in ferrets presented to Japanese veterinary hospitals. Both presented with pyogranulomatous inflammation in the abdominal cavity, and both cases tested positive for coronavirus antigen by IHC. In 1 case, for which unfixed tissues were available, FRSCV RNA was detected by reverse-transcriptase polymerase chain reaction in the affected tissues.
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http://dx.doi.org/10.1053/j.jepm.2014.02.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106053PMC
April 2014

Ocular and neural distribution of feline herpesvirus-1 during active and latent experimental infection in cats.

BMC Vet Res 2013 Sep 22;9:185. Epub 2013 Sep 22.

Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, D208 Veterinary Medical Center, 48824-1314 East Lansing, MI, USA.

Background: Herpes simplex virus 1 (HSV-1) and varicella zoster virus (VZV) cause extensive intra-ocular and neural infections in humans and are closely related to Felid herpes virus 1 (FeHV-1). We report the extent of intra-ocular replication and the extent and morphological aspects of neural replication during the acute and latent phases of FeHV-1 infection. Juvenile, SPF cats were inoculated with FeHV-1. Additional cats were used as negative controls. Cats were euthanized on days 6, 10, and 30 post-inoculation.

Results: FeHV-1 was isolated from the conjunctiva, cornea, uveal tract, retina, optic nerve, ciliary ganglion (CG), pterygopalatine ganglion (PTPG), trigeminal ganglion (TG), brainstem, visual cortex, cerebellum, and olfactory bulb of infected cats during the acute phase, but not the cranial cervical ganglion (CCG) and optic chiasm. Viral DNA was detected in all tissues during acute infection by a real-time quantitative PCR assay. On day 30, viral DNA was detected in all TG, all CCG, and 2 PTPG. Histologically mild inflammation and ganglion cell loss were noted within the TG during acute, but not latent infection. Using linear regression, a strong correlation existed between clinical score and day 30 viral DNA copy number within the TG.

Conclusions: The correlation between clinical score and day 30 viral DNA copy number suggests the severity of the acute clinical infection is related to the quantity of latent viral DNA. The histologic response was similar to that seen during HSV-1 or VZV infection. To the author's knowledge this is the first report of FeHV-1 infection involving intraocular structures and autonomic ganglia.
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http://dx.doi.org/10.1186/1746-6148-9-185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4016492PMC
September 2013

Papillomavirus-associated cutaneous papillomas in a population of wild spotted hyenas (Crocuta crocuta).

J Wildl Dis 2013 Jul;49(3):627-31

Pathology Department, MPI Research, Mattawan, Michigan 49071, USA.

Beginning in 1997 Michigan State University Mara Hyena Project investigators observed waxing and waning progression of oral and genital masses during long-term behavioral observations of a population of wild spotted hyenas (Crocuta crocuta) from the Masai Mara Game Reserve, Kenya. From 1999-2000, we darted adult spotted hyenas to obtain routine physiologic and hematologic data and collected small, raised, lobulated, pigmented masses from the oral or genital areas of eight animals. Microscopically, masses consisted of variably thickened epidermis with thick elongate rete pegs, prominent stratum spinosum, and few koilocytes, consistent with papillomavirus-induced lesions. Immunohistochemistry on formalin-fixed, paraffin-embedded papilloma tissue revealed positive intranuclear labeling for papillomavirus antigen in the superficial stratum granulosum and in sloughing keratin layers of multiple samples. Polymerase chain reaction on DNA extracts from tumor tissue amplified a papillomavirus-specific 418 base pair amplicon in the E1 ORF. Basic Local Alignment Search Tool analysis of the sequenced amplicon suggests a novel hyaenid papillomavirus. Confirmatory complete genomic sequencing was performed later by the Rega Institute in Belgium. To our knowledge, this is the first report of a papillomavirus in a Hyaenidae species. Spotted hyena social behavior might facilitate oral-genital transmission of papillomavirus in this population.
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http://dx.doi.org/10.7589/2011-09-262DOI Listing
July 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

Fatal Canid herpesvirus 1 infection in an adult dog.

J Vet Diagn Invest 2012 May;24(3):604-7

Diagnostic Center for Population and Animal Health, Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48910-8104, USA.

Canid herpesvirus 1 (CaHV-1) is a well-known cause of fatal hepatic and renal necrosis in neonatal puppies. In adult dogs infected with CaHV-1, papulovesicular genital lesions may be observed. CaHV-1 infection during pregnancy can lead to embryonic resorption, abortion, and stillbirth. In high-density dog populations, CaHV-1 can also contribute to kennel cough. Furthermore, recent literature has clearly documented that CaHV-1 can induce ocular disease in immature and adult dogs. The current study describes a case of fatal CaHV-1 infection in a 9-year-old spayed female Bichon Frise dog. Following a history of vomiting and diarrhea, the dog deteriorated and subsequently died. The main lesions were multifocal areas of necrosis with intranuclear inclusion bodies in the liver, adrenal gland, and small intestine, similar to the lesions observed in CaHV-1-infected puppies. Infection with CaHV-1 was confirmed on samples of liver by polymerase chain reaction, immunohistochemistry, and in situ hybridization. There was no indication of immunosuppression in this dog. Based on the results presented herein, CaHV-1 should be included in the list of differential diagnoses of hepatic necrosis in adult dogs.
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http://dx.doi.org/10.1177/1040638712440994DOI Listing
May 2012

Diagnostic sensitivity and specificity of in situ hybridization and immunohistochemistry for Eastern equine encephalitis virus and West Nile virus in formalin-fixed, paraffin-embedded brain tissue of horses.

J Vet Diagn Invest 2012 Mar;24(2):333-8

Diagnostic Center for Population and Animal Health, College of Veterinary Medicine, Michigan State University, Lansing, MI 48910, USA.

Immunohistochemistry (IHC) and in situ hybridization (ISH) can be used either to detect or to differentiate between Eastern equine encephalitis virus (EEEV) and West Nile virus (WNV) within formalin-fixed, paraffin-embedded (FFPE) brain tissue of horses. To compare the diagnostic sensitivity and specificity of ISH and IHC, FFPE brain tissue from 20 EEEV-positive horses and 16 WNV-positive horses were tested with both EEEV and WNV oligoprobes and EEEV- and WNV-specific antibodies. Reverse transcription polymerase chain reaction (RT-PCR) for detection of EEEV and WNV was used as the gold standard to confirm infection. All horses that tested positive for EEEV by RT-PCR also tested positive by IHC and ISH, except for 1 case that was false-negative by ISH. In contrast, all horses that tested positive for WNV by RT-PCR tested negative by IHC and only 2 horses tested positive by ISH. No false-positives were detected with either method for both viruses. Both IHC and ISH are highly specific and sensitive diagnostic methods to detect EEEV in equine FFPE brain tissues, although neither appear effective for the diagnosis of WNV in equine neurologic cases.
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http://dx.doi.org/10.1177/1040638711435230DOI Listing
March 2012

Canine reproductive, respiratory, and ocular diseases due to canine herpesvirus.

Vet Clin North Am Small Anim Pract 2011 Nov;41(6):1097-120

Department of Veterinary Clinical Sciences and Washington Animal Disease Diagnostic Laboratory, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA.

This review documents how clinical inquiry expands as our knowledge base about canine herpesvirus (CHV) increases. We must understand the various forms of CHV infection that may occur in the dog population. This has prompted the veterinary community to develop more sensitive diagnostic assays. CHV is more common than we considered a decade ago. Up to 70% of some high-risk dog populations have been infected with and are latent carriers of CHV. Recognition of the various forms of CHV-induced disease, availability of diagnostic assays with increased sensitivity, and the formation of reliable biosecurity measures will allow for better control steps.
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http://dx.doi.org/10.1016/j.cvsm.2011.08.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114841PMC
November 2011

Pseudorabies virus infection in Oklahoma hunting dogs.

J Vet Diagn Invest 2011 Sep;23(5):915-23

Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, , Oklahoma State University College of Veterinary Medicine, Stillwater, OK 74078, USA.

Pseudorabies is caused by Suid herpesvirus 1, a member of the Alphaherpesvirinae subfamily. Although pigs are the natural host of Pseudorabies virus (PRV), the virus has a broad host range and may cause fatal encephalitis in many species. The United States obtained PRV-free status in 2004 after the virus was eradicated from domestic swineherds, but the virus is still present in feral swine populations. The current report describes PRV infection in 3 dogs that were used to hunt feral swine. The dogs developed clinical signs including facial pruritus with facial abrasions, dyspnea, vomiting, diarrhea, ataxia, muscle stiffness, and death. Two were euthanized, and 1 died within approximately 48 hr after onset of clinical signs. The salient histologic changes consisted of neutrophilic trigeminal ganglioneuritis with neuronophagia and equivocal intranuclear inclusion bodies. Pseudorabies virus was isolated from fresh tissues from 2 of the dogs, and immunohistochemistry detected the virus in the third dog. Virus sequencing and phylogeny, based upon available GenBank sequences, revealed that the virus was likely a field strain that was closely related to a cluster of PRV strains previously identified in Illinois. Though eradicated from domestic swine in the United States, PRV is present in populations of feral swine, and should therefore continue to be considered a possible cause of disease in dogs and other domestic animals with compatible clinical history and signs. Continued surveillance is necessary to prevent reintroduction of PRV into domestic swine.
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http://dx.doi.org/10.1177/1040638711416628DOI Listing
September 2011

Ferret coronavirus-associated diseases.

Vet Clin North Am Exot Anim Pract 2010 Sep;13(3):543-60

Animal Clinic of Farmers Branch, 14021 Denton Drive, Dallas, TX 75234, USA.

A novel coronavirus of ferrets was first described in 1993. This coronavirus caused an enteric disease called epizootic catarrhal enteritis (ECE). Recently, a ferret systemic coronavirus (FRSCV)-associated disease was discovered. This new systemic disease resembles the dry form of feline infectious peritonitis (FIP) and has been reported in the United States and Europe. This article addresses the clinical signs, pathology, pathogenesis, diagnosis, treatment, and prevention of this ferret FIP-like disease.
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http://dx.doi.org/10.1016/j.cvex.2010.05.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110453PMC
September 2010

Complete genomic sequence and an infectious BAC clone of feline herpesvirus-1 (FHV-1).

Virology 2010 Jun 21;401(2):215-27. Epub 2010 Mar 21.

Graduate Program in Comparative Medicine and Integrative Biology, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.

Infection with feline herpesvirus-1 (FHV-1) is a major cause of upper respiratory and ocular diseases in Felidae. We report the first complete genomic sequence of FHV-1, as well as the construction and characterization of a bacterial artificial chromosome (BAC) clone of FHV-1, which contains the entire FHV-1 genome and has the BAC vector inserted at the left end of U(L). Complete genomic sequences were derived from both the FHV-1 BAC clone and purified virion DNA. The FHV-1 genome is 135,797bp in size with an overall G+C content of 45%. A total of 78 open reading frames were predicted, encoding 74 distinct proteins. The gene arrangement is collinear with that of most sequenced varicelloviruses. The virus regenerated from the BAC was very similar to the parental C-27 strain in vitro in terms of plaque morphology and growth characteristics and highly virulent in cats in a preliminary in vivo study.
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http://dx.doi.org/10.1016/j.virol.2010.02.021DOI Listing
June 2010

Comparative sequence analysis of the distal one-third of the genomes of a systemic and an enteric ferret coronavirus.

Virus Res 2010 Apr 15;149(1):42-50. Epub 2010 Jan 15.

Diagnostic Center for Population and Animal Health, 4125 Beaumont Road, Lansing, MI 48909, USA.

Ferret systemic coronavirus (FRSCV) infection is associated with an emerging, highly fatal disease of ferrets. Enhanced macrophage tropism and the resulting induction of pyogranulomatous lesions are shared with feline infectious peritonitis virus (FIPV) infection in cats, but are not features of ferret enteric coronavirus (FRECV) infection. Comparative sequence analysis of the distal one-third of the genomes of one FRSCV and one FRECV strain showed that these two ferret coronaviruses share >96% nucleotide sequence identities in the membrane (M), nucleocapsid (N) and non-structural protein genes (partial polymerase, open reading frames [ORFs] 3 and 7b). The envelope (E) protein gene showed a moderate nucleotide sequence similarity of 91.6%. In contrast, nucleotide and amino acid sequence similarities observed with the spike (S) protein were only 79.5 and 79.6%, respectively. Twenty-one amino acid differences within a 195-199-amino acid C-terminal portion of the S protein were conserved between 3 strains each of FRSCV and FRECV. Both systemic and enteric strains were found to carry a single ORF 3 gene with truncated proteins observed in two out of three FRSCV strains examined. The two enteric strains analyzed each contained an intact ORF 3 gene. Phylogenetically, FRSCV is more closely related to FRECV than to other group 1 coronaviruses.
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http://dx.doi.org/10.1016/j.virusres.2009.12.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114374PMC
April 2010

Novel calicivirus identified in rabbits, Michigan, USA.

Emerg Infect Dis 2009 Dec;15(12):1955-62

University of Michigan, Unit for Laboratory Animal Medicine, 1150 W Medical Center Drive, Ann Arbor, MI 48109, USA.

We report a disease outbreak in a Michigan rabbitry of a rabbit calicivirus distinct from the foreign animal disease agent, rabbit hemorrhagic disease virus (RHDV). The novel virus has been designated Michigan rabbit calicivirus (MRCV). Caliciviruses of the Lagovirus genus other than RHDV have not been described in US rabbit populations. The case-fatality rate was 32.5% (65/200). Clinical signs included hemorrhage and sudden death, with hepatic necrosis. Analysis of viral RNA sequence from >95% of the viral genome showed an average similarity of 79% with RHDV. Similarity of the predicted MRCV capsid amino acid sequence ranged from 89.8% to 91.3%, much lower than the 98% amino acid similarity between RHDV strains. Experimentally infected rabbits lacked clinical disease, but MRCV was detected in tissues by PCR. We propose that MRCV primarily causes subclinical infection but may induce overt RHD-like disease under certain field conditions.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044539PMC
http://dx.doi.org/10.3201/eid1512.090839DOI Listing
December 2009

Clinical, histologic, and immunohistochemical characterization of wart-like lesions on the paw pads of dogs: 24 cases (2000-2007).

J Am Vet Med Assoc 2009 Jun;234(12):1555-8

Department of Veterinary Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA 01536, USA.

OBJECTIVE- To determine clinical, histologic, and immunohistochemical findings for dogs with wart-like lesions involving the paw pads. DESIGN- Retrospective case series. ANIMALS- 24 dogs (18 Greyhounds and 6 dogs of other breeds). PROCEDURES- Medical records were reviewed for information on signalment, physical examination findings, concurrent disease processes, location of all lesions, and, when available, results of histologic examination of biopsy specimens. Available biopsy specimens (n = 11) were submitted for immunohistochemical staining and a PCR assay to identify viral inclusion bodies. RESULTS- In Greyhounds, most lesions involved the pads of the third and fourth digits, had a consistent histologic appearance without evidence of inflammation, were negative for papillomavirus, and had an unsatisfactory response to treatment. In other breeds, lesions often involved the pads of non-weight-bearing digits, had histologic evidence of inflammation, were positive for papillomavirus, and responded to surgical treatment. CONCLUSIONS AND CLINICAL RELEVANCE- Results suggested that wart-like lesions involving the paw pads of Greyhounds were a distinct clinical entity with features resembling porokeratosis plantaris discreta in humans. In Greyhounds, these lesions were not associated with an underlying viral etiology and, therefore, should not be considered plantar warts. Alternative treatments should be investigated because current treatments were generally unsuccessful in Greyhounds. Wart-like lesions of the paw pads in other breeds were often associated with papillomavirus, and surgical excision appeared curative.
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http://dx.doi.org/10.2460/javma.234.12.1555DOI Listing
June 2009

New hosts for equine herpesvirus 9.

Emerg Infect Dis 2008 Oct;14(10):1616-9

Zoological Society of San Diego, Wildlife Disease Laboratories, Escondido, California 92027, USA.

Equine herpesvirus 9 was detected in a polar bear with progressive encephalitis; the source was traced to 2 members of a potential equid reservoir species, Grevy's zebras. The virus was also found in an aborted Persian onager. Thus, the natural host range is extended to 6 species in 3 mammalian orders.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2609862PMC
http://dx.doi.org/10.3201/eid1410.080703DOI Listing
October 2008

Infection with Aleutian disease virus-like virus in a captive striped skunk.

J Am Vet Med Assoc 2008 Mar;232(5):742-6

Department of Small Animal Clinical Services, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.

Case Description: A 5-month-old captive female striped skunk (Mephitis mephitis) was evaluated because of lethargy, signs of depression, azotemia, and erythema of the skin around the eyes.

Clinical Findings: Antemortem diagnostic tests revealed renal disease but failed to identify an etiologic agent. A diagnosis of severe nonsuppurative interstitial nephritis was made on the basis of results of histologic examination of renal biopsy specimens.

Treatment And Outcome: The skunk was administered isotonic fluids SC daily and later every other day because of the handling-related stress. Because of the skunk's deteriorating condition, it was euthanized after 24 days of supportive care. Aleutian disease was diagnosed on the basis of positive results of a PCR assay that targeted the DNA from Aleutian disease virus (ADV); positive results for ADV were also obtained by use of plasma counterimmunoelectrophoresis and an ELISA. Genetic sequencing of the 365-base pair PCR product revealed 90% sequence identity with mink ADV.

Clinical Relevance: In the skunk of this report, infection with a skunk-specific parvovirus resulted in clinical signs and pathologic changes similar to those associated with ADV infection in mink. For skunks with signs of renal failure, differential diagnoses should include parvovirus infection. In confirmed cases of infection with this ADV-like virus, appropriate quarantine and biosecurity measures should be in place to prevent spread to other susceptible animals within a zoological collection.
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http://dx.doi.org/10.2460/javma.232.5.742DOI Listing
March 2008

An outbreak of Eastern equine encephalitis virus in free-ranging white-tailed deer in Michigan.

J Wildl Dis 2007 Oct;43(4):635-44

Wildlife Disease Laboratory, Michigan Department of Natural Resources, 4125 Beaumont Rd., Room 250, Lansing, Michigan 48910-8106, USA.

Eastern equine encephalitis (EEE) virus has been recognized as affecting horses and humans in the eastern United States for 70 yr. Evidence of exposure with EEE virus has been reported in a variety of free-ranging wild birds and mammals but cases of clinical disease are much less commonly reported. In Michigan, reports of outbreaks of EEE virus in equine species extend back more than a half century. We report diagnosis of EEE virus infection of multiple free-ranging white-tailed deer (Odocoileus virginianus) from three Michigan counties during late summer of 2005. Infection was confirmed in seven of 30 deer collected based on reported neurologic signs and results from immunohistochemistry, polymerase chain reaction, and/or virus isolation. One of the deer also was infected with West Nile virus and an eighth deer had microscopic lesions in the cerebrum consistent with those reported for EEE. To our knowledge, this is the first report of multiple cases of EEE in free-ranging white-tailed deer, and highlights several issues of significance to wildlife managers and public health officials.
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http://dx.doi.org/10.7589/0090-3558-43.4.635DOI Listing
October 2007

Systemic calicivirus epidemic in captive exotic felids.

J Zoo Wildl Med 2007 Jun;38(2):292-9

Potter Park Zoo, 1301 South Pennsylvania, Lansing, Michigan 48912, USA.

A 5-day-old, mother-raised, Amur tiger cub (Panthera tigris altaica) presented with tongue ulcerations. Identical lesions appeared and progressed to sloughing of the tongue in the three littermates of this cub the following day. The lesions progressed in all cubs to include sloughing of the carpal, tarsal, metacarpal, and metatarsal foot pad epithelium. Oral ulcerations were also noted in adult African lions (Panthera leo) and Amur tigers (Panthera tigris altaica), but not in two adult snow leopards (Panthera uncia) housed in the same building. All adult cats had been previously vaccinated for common feline diseases including feline calicivirus (FCV). Detection of FCV RNA in oral secretions by a real-time reverse transcription polymerase chain reaction assay (RRT-PCR) confirmed FCV infection in the tiger cubs and one lion. A male lion and a male tiger cub died during the disease outbreak. RRT-PCR confirmed FCV in multiple tissues in both of these animals. A stray cat live-trapped outside the feline building during the epidemic was found to be positive for FCV by virus isolation and was thought to be the source of infection.
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http://dx.doi.org/10.1638/1042-7260(2007)038[0292:SCEICE]2.0.CO;2DOI Listing
June 2007

Evaluation of tongue as a complementary sample for the diagnosis of parvoviral infection in dogs and cats.

J Vet Diagn Invest 2007 Jul;19(4):409-13

Diagnostic Center for Population and Animal Health, Michigan State University, Lansing, MI 48910, USA.

Diagnosis of canine parvovirus type 2 and feline panleukopenia virus infection in dogs and cats may be hampered by the severity of enteric lesions, secondary bacterial overgrowth, and rapid onset of autolysis. In contrast to small intestine, tongue epithelium is less sensitive to postmortem changes. Sections of tongue and small intestine from 11 dogs and 11 cats with a clinical history and gross and microscopic lesions compatible with canine and feline parvoviral infection were examined for parvoviral infection using real-time polymerase chain reaction (PCR), immunohistochemistry (IHC), and direct fluorescent antibody testing (FA). Parvoviral DNA was detected by PCR in both small intestine and tongue of all but 1 dog. Nineteen of 22 animals (86%) with suspect or positive FA staining in the small intestine also had positive FA and IHC staining in the tongue. Three of 3 dogs (100%) whose carcasses had been frozen and thawed prior to necropsy had more consistently positive staining in tongue than in small intestine by FA and IHC. These data confirm tongue as an excellent complementary sample for parvoviral testing in dogs and cats, especially in cases in which postmortem autolysis has occurred.
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http://dx.doi.org/10.1177/104063870701900413DOI Listing
July 2007