This page has only limited features, please log in for full access.
Caprine arthritis encephalitis virus (CAEV) is a monocyte/macrophage-tropic lentivirus that primarily infects goats resulting in a well-recognized set of chronic inflammatory syndromes focused on the joint synovium, tissues of the central nervous system, pulmonary interstitium and mammary gland. Clinically affected animals generally manifest with one or more of these classic CAEV-associated tissue lesions; however, CAEV-associated renal inflammation in goats has not been reported in the peer-reviewed literature. Here we describe six goats with chronic, multisystemic CAEV infections in conjunction with CAEV-associated renal lesions. One of the animals had CAEV antigen-associated thrombotic arteritis resulting in infarction of both the kidney and heart. These goats had microscopic evidence of inflammatory renal injury (interstitial nephritis) with detectable renal immunolabeling for CAEV antigen in three of six animals and amplifiable proviral sequences consistent with CAEV in all six animals. Cardiac lesions (vascular, myocardial or endocardial) were also identified in four of six animals. Within the viral promoter (U3) region, known transcription factor binding sites (TFBSs) were generally conserved, although one viral isolate had a duplication of the U3 A region encoding a second gamma-activated site (GAS). Despite the TFBS conservation, the isolates demonstrated a degree of phylogenetic diversity. At present, the clinical consequence of CAEV-associated renal injury is not clear.
Brian Murphy; Diego Castillo; Asli Mete; Helena Vogel; Dayna Goldsmith; Marietta Barro; Omar Gonzales-Viera. Caprine Arthritis Encephalitis Virus Is Associated with Renal Lesions. Viruses 2021, 13, 1051 .
AMA StyleBrian Murphy, Diego Castillo, Asli Mete, Helena Vogel, Dayna Goldsmith, Marietta Barro, Omar Gonzales-Viera. Caprine Arthritis Encephalitis Virus Is Associated with Renal Lesions. Viruses. 2021; 13 (6):1051.
Chicago/Turabian StyleBrian Murphy; Diego Castillo; Asli Mete; Helena Vogel; Dayna Goldsmith; Marietta Barro; Omar Gonzales-Viera. 2021. "Caprine Arthritis Encephalitis Virus Is Associated with Renal Lesions." Viruses 13, no. 6: 1051.
X-linked hypohidrotic ectodermal dysplasia-1 (ECTD1) in people results in a spectrum of abnormalities, most importantly hypotrichosis, anodontia/oligodontia, and absent or defective ectodermally derived glands. Five Red Angus-Simmental calves born over a 6-year period demonstrated severe hypotrichosis and were diagnosed as affected with ECTD1-like syndrome. Two died of severe pneumonia within a week of birth. The skin of three affected calves revealed a predominance of histologically unremarkable small-caliber hair follicles. Larger follicles (>50 µm) containing medullated hairs (including guard and tactile hairs) were largely restricted to the muzzle, chin, tail, eyelids, tragus and distal portions of the limbs and tail. The mean histological density of hair follicles in flank skin of two affected calves was slightly greater than that in two unaffected calves. One affected calf was examined postmortem at 10 days of age to better characterize systemic lesions. Nasolabial, intranasal and tracheobronchial mucosal glands were absent, whereas olfactory glands were unaffected. Mandibular incisor teeth were absent. Premolar teeth were unerupted and widely spaced. Other than oligodontia, histological changes in teeth were modest, featuring multifocal disorganization of ameloblasts, new bone formation in dental alveoli, and small aggregates of osteodentin and cementum at the margins of the enamel organ. A 52,780 base pair deletion spanning six out of eight coding exons of EDA and all of AWAT2 was identified. Partial deletion of the EDA gene is the presumed basis for the reported X-chromosomal recessive inherited genodermatosis.
Donal O’Toole; Irene Häfliger; Fabienne Leuthard; Brant Schumaker; Lynn Steadman; Brian Murphy; Cord Drögemüller; Tosso Leeb. X-Linked Hypohidrotic Ectodermal Dysplasia in Crossbred Beef Cattle Due to a Large Deletion in EDA. Animals 2021, 11, 657 .
AMA StyleDonal O’Toole, Irene Häfliger, Fabienne Leuthard, Brant Schumaker, Lynn Steadman, Brian Murphy, Cord Drögemüller, Tosso Leeb. X-Linked Hypohidrotic Ectodermal Dysplasia in Crossbred Beef Cattle Due to a Large Deletion in EDA. Animals. 2021; 11 (3):657.
Chicago/Turabian StyleDonal O’Toole; Irene Häfliger; Fabienne Leuthard; Brant Schumaker; Lynn Steadman; Brian Murphy; Cord Drögemüller; Tosso Leeb. 2021. "X-Linked Hypohidrotic Ectodermal Dysplasia in Crossbred Beef Cattle Due to a Large Deletion in EDA." Animals 11, no. 3: 657.
Odontogenic lesions are well described in domestic cats, but published literature describing these lesions in nondomestic felids is limited. This study reports oral lesions in 109 captive, non-domestic felids. Ten cases of odontogenic lesions were diagnosed, including 9 with fibromatous epulis of periodontal ligament origin (FEPLO) and one odontogenic cyst in a cougar. FEPLO was common in lions. FEPLO did not recur after surgical removal in any of the 3 cases for which follow-up information was available. Increased occurrences of oral papillomas in snow leopards and eosinophilic granulomas in tigers were identified, which is consistent with the reported literature. With the exception of oral papillomas in snow leopards and FEPLO in lions, the spectrum of oral lesions in nondomestic felids was similar to what is reported in domestic cats, with squamous cell carcinoma being the most common oral malignancy, and stomatitis/gingivitis/glossitis accounting for approximately one third of all cases. Rare diagnoses with one case each included hemangioma, fibrosarcoma, melanoma, cleft palate, and glossal amyloidosis.
Katherine L. Scott; Michael M. Garner; Brian G. Murphy; Elise E. B. Ladouceur. Oral Lesions in Captive Nondomestic Felids With a Focus on Odontogenic Lesions. Veterinary Pathology 2020, 57, 880 -884.
AMA StyleKatherine L. Scott, Michael M. Garner, Brian G. Murphy, Elise E. B. Ladouceur. Oral Lesions in Captive Nondomestic Felids With a Focus on Odontogenic Lesions. Veterinary Pathology. 2020; 57 (6):880-884.
Chicago/Turabian StyleKatherine L. Scott; Michael M. Garner; Brian G. Murphy; Elise E. B. Ladouceur. 2020. "Oral Lesions in Captive Nondomestic Felids With a Focus on Odontogenic Lesions." Veterinary Pathology 57, no. 6: 880-884.
Coronaviruses are enveloped RNA viruses capable of causing respiratory, enteric, or systemic diseases in a variety of mammalian hosts that vary in clinical severity from subclinical to fatal. The host range and tissue tropism are largely determined by the coronaviral spike protein, which initiates cellular infection by promoting fusion of the viral and host cell membranes. Companion animal coronaviruses responsible for causing enteric infection include feline enteric coronavirus, ferret enteric coronavirus, canine enteric coronavirus, equine coronavirus, and alpaca enteric coronavirus, while canine respiratory coronavirus and alpaca respiratory coronavirus result in respiratory infection. Ferret systemic coronavirus and feline infectious peritonitis virus, a mutated feline enteric coronavirus, can lead to lethal immuno-inflammatory systemic disease. Recent human viral pandemics, including severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and most recently, COVID-19, all thought to originate from bat coronaviruses, demonstrate the zoonotic potential of coronaviruses and their potential to have devastating impacts. A better understanding of the coronaviruses of companion animals, their capacity for cross-species transmission, and the sharing of genetic information may facilitate improved prevention and control strategies for future emerging zoonotic coronaviruses. This article reviews the clinical, epidemiologic, virologic, and pathologic characteristics of nine important coronaviruses of companion animals.
Christine Haake; Sarah Cook; Nicola Pusterla; Brian Murphy. Coronavirus Infections in Companion Animals: Virology, Epidemiology, Clinical and Pathologic Features. Viruses 2020, 12, 1023 .
AMA StyleChristine Haake, Sarah Cook, Nicola Pusterla, Brian Murphy. Coronavirus Infections in Companion Animals: Virology, Epidemiology, Clinical and Pathologic Features. Viruses. 2020; 12 (9):1023.
Chicago/Turabian StyleChristine Haake; Sarah Cook; Nicola Pusterla; Brian Murphy. 2020. "Coronavirus Infections in Companion Animals: Virology, Epidemiology, Clinical and Pathologic Features." Viruses 12, no. 9: 1023.
Four captive, lesser hedgehog tenrecs ( Echinops telfairi) were euthanized for soft bones that prevented normal mastication and/or ambulation. Antemortem radiographs (available in 2 cases) revealed osteopenia. Antemortem bloodwork (available in 2 cases) revealed hypophosphatemia. Dietary history (available in 2 cases) indicated the animals were eating only insects. Histologically, all examined bones had wide osteoid seams that caused expansion of the cortices. Osteoid deposition was exuberant and it partially filled marrow cavities (hyperostosis). Nondecalcified sections of bone (available in 2 cases) revealed that osteoid was poorly mineralized, consistent with osteomalacia. Insects are poor dietary sources of vitamin D, and dietary vitamin D deficiency is considered the most likely cause for metabolic bone disease in these animals.
Elise E. B. Ladouceur; Brian G. Murphy; Michael M. Garner; Andrew N. Cartoceti. Osteomalacia With Hyperostosis in Captive Lesser Hedgehog Tenrecs (Echinops telfairi). Veterinary Pathology 2020, 57, 885 -888.
AMA StyleElise E. B. Ladouceur, Brian G. Murphy, Michael M. Garner, Andrew N. Cartoceti. Osteomalacia With Hyperostosis in Captive Lesser Hedgehog Tenrecs (Echinops telfairi). Veterinary Pathology. 2020; 57 (6):885-888.
Chicago/Turabian StyleElise E. B. Ladouceur; Brian G. Murphy; Michael M. Garner; Andrew N. Cartoceti. 2020. "Osteomalacia With Hyperostosis in Captive Lesser Hedgehog Tenrecs (Echinops telfairi)." Veterinary Pathology 57, no. 6: 885-888.
Feline infectious peritonitis (FIP), caused by a genetic mutant of feline enteric coronavirus known as FIPV, is a highly fatal disease of cats with no currently available vaccine or FDA-approved cure. Dissemination of FIPV in affected cats results in a range of clinical signs including cavitary effusions, anorexia, fever and lesions of pyogranulomatous vasculitis and peri-vasculitis with or without central nervous system and/or ocular involvement. There is a critical need for effective and approved antiviral therapies against coronaviruses including FIPV and zoonotic coronaviruses such as SARS-CoV-2, the cause of COVID-19. With regards to SARS-CoV-2, preliminary evidence suggests that there may be potential clinical and pathological overlap with feline coronaviral disease including enteric and neurological involvement in some cases. We have screened 89 putative antiviral compounds and have identified 25 compounds with antiviral activity against FIPV, representing a variety of drug classes and mechanisms of antiviral action. Based upon successful combination treatment strategies for human patients with HIV or hepatitis C virus infections, we have identified combinations of drugs targeting different steps of the FIPV life cycle resulting in synergistic antiviral effect. Translationally, we suggest that a combined anticoronaviral therapy (cACT) with multiple mechanisms of action and penetration of all potential anatomic sites of viral infection should be applied towards other challenging to treat coronaviruses, like SARS-CoV-2.
Sarah Cook; Helena Vogel; Luis Diego Castillo; Mark Olsen; Niels Pedersen; Brian G Murphy. A rational approach to identifying effective combined anticoronaviral therapies against feline coronavirus. 2020, 1 .
AMA StyleSarah Cook, Helena Vogel, Luis Diego Castillo, Mark Olsen, Niels Pedersen, Brian G Murphy. A rational approach to identifying effective combined anticoronaviral therapies against feline coronavirus. . 2020; ():1.
Chicago/Turabian StyleSarah Cook; Helena Vogel; Luis Diego Castillo; Mark Olsen; Niels Pedersen; Brian G Murphy. 2020. "A rational approach to identifying effective combined anticoronaviral therapies against feline coronavirus." , no. : 1.
Modern antiretroviral therapy for immunodeficiency viruses, although remarkably effective in controlling viral transcription, and overt virus-associated morbidity, has failed to absolutely eradicate retroviruses from their infected hosts as a result of proviral integration in long-lived reservoir cells. Immunodeficiency virus-infected patients are therefore consigned to lifelong antiviral therapy as a means to control viremia, viral transmission, and infection-associated morbidity. Unfortunately, lifelong antiviral therapies can be difficult for patients to continuously maintain and may be associated with therapy-specific morbidities. Patient advocates have argued for new methods to achieve retroviral eradication. As a proof-of-concept study, a lentivirus-delivered RNA-directed gene editing strategy was utilized in a series of in vitro experiments in an attempt to attenuate the feline immunodeficiency virus (FIV) proviral load, viral transcription, and production of infectious virions. We found that a feline T lymphocyte cell line (MCH5-4) treated with an FIV-specific clustered regularly interspersed short palindromic repeats (CRISPR)-associated protein 9 (Cas9) gene editing tool resulted in a reduction of cell-free viral RNA relative to control cells. Decreased infectious potential was demonstrated in a two-step FIV infection study—naïve MCH5-4 cells infected with cell-free FIV harvested from FIV-infected and CRISPR lentivirus-treated cells had less integrated proviral DNA than control cells. This study represents the initial steps towards the development of an effective method of proviral eradication in an immunodeficiency virus-infected host.
Brian G. Murphy; Tatiana Wolf; Helena Vogel; Diego Castillo; Kevin Woolard. An RNA-Directed Gene Editing Strategy for Attenuating the Infectious Potential of Feline Immunodeficiency Virus-Infected Cells: A Proof of Concept. Viruses 2020, 12, 511 .
AMA StyleBrian G. Murphy, Tatiana Wolf, Helena Vogel, Diego Castillo, Kevin Woolard. An RNA-Directed Gene Editing Strategy for Attenuating the Infectious Potential of Feline Immunodeficiency Virus-Infected Cells: A Proof of Concept. Viruses. 2020; 12 (5):511.
Chicago/Turabian StyleBrian G. Murphy; Tatiana Wolf; Helena Vogel; Diego Castillo; Kevin Woolard. 2020. "An RNA-Directed Gene Editing Strategy for Attenuating the Infectious Potential of Feline Immunodeficiency Virus-Infected Cells: A Proof of Concept." Viruses 12, no. 5: 511.
Odontomas are variably differentiated, hamartoma-like proliferations of odontogenic epithelium, pulp ectomesenchyme (odontoblasts), and dental matrix. Frogs are polyphyodont and homodont. Their teeth also differ from mammals in that they are restricted to the upper jaw in adults and lack a periodontal ligament and cementum, attaching directly to the underlying bone. Odontomas were identified in an African clawed frog ( Xenopus laevis), a false tomato frog ( Dyscophus guineti), and a tomato frog of unknown species ( Dyscophus sp.). All of the examined odontomas were composed of numerous tooth-like structures comprising an arc of dentinal matrix lined on the convex surface by ameloblasts and on the concave surface by odontoblasts. Masson’s trichrome and immunohistochemistry with pan-cytokeratin supported these findings. The pathogenesis of these lesions may be displacement of the dental lamina, which has been shown in research studies to lead to de novo proliferation of dental elements in frogs.
Elise E. B. Ladouceur; Amanda M. Hauck; Michael M. Garner; Andrew N. Cartoceti; Brian G. Murphy. Odontomas in Frogs. Veterinary Pathology 2019, 57, 147 -150.
AMA StyleElise E. B. Ladouceur, Amanda M. Hauck, Michael M. Garner, Andrew N. Cartoceti, Brian G. Murphy. Odontomas in Frogs. Veterinary Pathology. 2019; 57 (1):147-150.
Chicago/Turabian StyleElise E. B. Ladouceur; Amanda M. Hauck; Michael M. Garner; Andrew N. Cartoceti; Brian G. Murphy. 2019. "Odontomas in Frogs." Veterinary Pathology 57, no. 1: 147-150.
Chondrodystrophy results in predictable and progressive biochemical and structural changes to the intervertebral disc, resulting in early onset degeneration and dystrophic mineralization of the disc. Accelerated degeneration and mineralization of the intervertebral disc are common in multiple dog breeds and can result in compromised function, herniation, pain, and a variety of neurological sequelae. A mutation responsible for chondrodystrophy in dogs has been identified as an aberrant fibroblast growth factor 4 (FGF4) retrogene insertion on chromosome 12 (CFA12) and is associated with short stature of the Nova Scotia Duck Tolling Retriever. Segregation of the CFA12 FGF4 retrogene in this dog breed provides an opportunity to examine the effect of retrogene presence on radiographic and histologic appearance of chondrodystrophic disc degeneration within a single breed. Here we found that in the intervertebral discs isolated from 2 dogs with the CFA12 FGF4 genotype, the nucleus pulposus was largely replaced by cartilaginous tissue, and physaliferous notochordal cells were rarely if ever identified. These findings are in contrast to the normal histologic findings in 2 breed-matched dogs lacking the mutation. The findings are consistent with premature chondroid degeneration of the intervertebral disc and suggest that the presence of the CFA12 FGF4 retrogene is sufficient to cause the chondrodystrophic phenotype.
Brian G. Murphy; Peter Dickinson; Denis J. Marcellin-Little; Kevin Batcher; Stephen Raverty; Danika Bannasch. Pathologic Features of the Intervertebral Disc in Young Nova Scotia Duck Tolling Retrievers Confirms Chondrodystrophy Degenerative Phenotype Associated With Genotype. Veterinary Pathology 2019, 56, 895 -902.
AMA StyleBrian G. Murphy, Peter Dickinson, Denis J. Marcellin-Little, Kevin Batcher, Stephen Raverty, Danika Bannasch. Pathologic Features of the Intervertebral Disc in Young Nova Scotia Duck Tolling Retrievers Confirms Chondrodystrophy Degenerative Phenotype Associated With Genotype. Veterinary Pathology. 2019; 56 (6):895-902.
Chicago/Turabian StyleBrian G. Murphy; Peter Dickinson; Denis J. Marcellin-Little; Kevin Batcher; Stephen Raverty; Danika Bannasch. 2019. "Pathologic Features of the Intervertebral Disc in Young Nova Scotia Duck Tolling Retrievers Confirms Chondrodystrophy Degenerative Phenotype Associated With Genotype." Veterinary Pathology 56, no. 6: 895-902.
Our laboratory has serially reported on the virologic and immunopathologic features of a cohort of experimental feline immunodeficiency virus (FIV)-infected cats for more than eight years. At 8.09 years post infection (PI), one of these animals entered the terminal stage of infection, characterized by undulating hyperthermia, progressive anorexia, weight loss, and pancytopenia; the animal was not responsive to therapeutic interventions, necessitating euthanasia six weeks later (8.20 years PI). Subsequent analyses indicated that neoplastic lymphocytes infiltrated multiple cervical lymph nodes and a band-like region of the mucosal lamina propria within a segment of the intestine. Immunohistochemistry and T cell clonality testing determined that the nodal and intestinal lesions were independently arising from CD3 T cell lymphomas. In-situ RNA hybridization studies indicated that diffuse neoplastic lymphocytes from the cervical lymph node contained abundant viral nucleic acid, while viral nucleic acid was not detectable in lymphocytes from the intestinal lymphoma lesion. The proviral long terminal repeat (LTR) was amplified and sequenced from multiple anatomic sites, and a common clone containing a single nucleotide polymorphism was determined to be defective in response to phorbol myristate acetate (PMA)-mediated promoter activation in a reporter gene assay. This assay revealed a previously unidentified PMA response element within the FIV U3 region 3’ to the TATA box. The possible implications of these results on FIV-lymphoma pathogenesis are discussed.
Brian G. Murphy; Christina Eckstrand; Diego Castillo; Andre Poon; Molly Liepnieks; Kristy Harmon; Peter Moore. Multiple, Independent T Cell Lymphomas Arising in an Experimentally FIV-Infected Cat during the Terminal Stage of Infection. Viruses 2018, 10, 280 .
AMA StyleBrian G. Murphy, Christina Eckstrand, Diego Castillo, Andre Poon, Molly Liepnieks, Kristy Harmon, Peter Moore. Multiple, Independent T Cell Lymphomas Arising in an Experimentally FIV-Infected Cat during the Terminal Stage of Infection. Viruses. 2018; 10 (6):280.
Chicago/Turabian StyleBrian G. Murphy; Christina Eckstrand; Diego Castillo; Andre Poon; Molly Liepnieks; Kristy Harmon; Peter Moore. 2018. "Multiple, Independent T Cell Lymphomas Arising in an Experimentally FIV-Infected Cat during the Terminal Stage of Infection." Viruses 10, no. 6: 280.
Osteosarcoma (OSA) is a common malignant bone tumor of large breed dogs that occurs at predictable anatomic sites. At the time of initial diagnosis, most affected dogs have occult pulmonary metastases. Even with aggressive surgical treatment combined with chemotherapy, the majority of dogs diagnosed with OSA live less than 1 year from the time of diagnosis. The ability to identify canine OSA cases most responsive to treatment is needed. In humans, OSA is also an aggressive tumor that is histologically and molecularly similar to canine OSA. The expression of the tumor suppressor gene product P16 by human OSA tissue has been linked to a favorable response to chemotherapy. We identified an antibody that binds canine P16 and developed a canine OSA tissue microarray in order to test the hypothesis that P16 expression by canine OSA tissue is predictive of clinical outcome following amputation and chemotherapy. Although statistical significance was not reached, a trend was identified between the lack of canine OSA P16 expression and a shorter disease free interval. The identification of a molecular marker for canine OSA is an important goal and the results reported here justify a larger study.
B. G. Murphy; M. Y. Mok; D. York; R. Rebhun; K. D. Woolard; C. Hillman; P. Dickinson; K. Skorupski. Evaluation of P16 expression in canine appendicular osteosarcoma. BMC Veterinary Research 2017, 13, 1 -9.
AMA StyleB. G. Murphy, M. Y. Mok, D. York, R. Rebhun, K. D. Woolard, C. Hillman, P. Dickinson, K. Skorupski. Evaluation of P16 expression in canine appendicular osteosarcoma. BMC Veterinary Research. 2017; 13 (1):1-9.
Chicago/Turabian StyleB. G. Murphy; M. Y. Mok; D. York; R. Rebhun; K. D. Woolard; C. Hillman; P. Dickinson; K. Skorupski. 2017. "Evaluation of P16 expression in canine appendicular osteosarcoma." BMC Veterinary Research 13, no. 1: 1-9.
Odontoameloblastoma (OA) is a mixed odontogenic tumor that is an ameloblastoma with concurrent histologic evidence of odontoma differentiation. As a mixed tumor, OA is a tripartite lesion comprised of neoplastic odontogenic epithelium, induced dental ectomesenchyme (dental pulp), and mineralized dental matrix. Although rare, OA represents a diagnostic conundrum, as it is histologically closely related to 2 other mixed odontogenic tumors: odontoma (complex and compound) and ameloblastic fibro-odontoma. Herein we describe an OA arising from the mandible of a 4-mo-old Fischer 344 rat that had been exposed in utero to the mutagen ENU (N-ethyl-N-nitrosourea), and a naturally occurring lesion in a 2-y-old Appaloosa horse. In order to satisfy the diagnostic criteria for this lesion, mineralized dental matrix in relationship to neoplastic odontogenic epithelium must be identifiable within the OA lesion. This group of odontogenic tumors is differentiated by the degree to which the dental matrix is organized and the relative proportions of pulp ectomesenchyme, odontogenic matrix, and odontogenic epithelium.
Brian Murphy; Cynthia Bell; Amanda Koehne; Richard R. Dubielzig. Mandibular odontoameloblastoma in a rat and a horse. Journal of Veterinary Diagnostic Investigation 2017, 29, 536 -540.
AMA StyleBrian Murphy, Cynthia Bell, Amanda Koehne, Richard R. Dubielzig. Mandibular odontoameloblastoma in a rat and a horse. Journal of Veterinary Diagnostic Investigation. 2017; 29 (4):536-540.
Chicago/Turabian StyleBrian Murphy; Cynthia Bell; Amanda Koehne; Richard R. Dubielzig. 2017. "Mandibular odontoameloblastoma in a rat and a horse." Journal of Veterinary Diagnostic Investigation 29, no. 4: 536-540.
A cutaneous proliferative mass was identified arising from the caudal peduncle of a captive neon tetra fish (Paracheirodon innesi). The lesion was histologically consistent with an ossifying fibroma (OF), a fibro-osseous proliferative lesion typically identified in the jaws or tooth-associated supportive tissues of mammals. Although it has been previously reported, there is no recent report of this lesion occurring in a fish. This is the first report of a cutaneous ossifying fibroma in a characin fish. The authors speculate on the pathogenesis of this lesion, which may have arisen from the scale-associated mesenchymal tissues.
B. Murphy; D.M. Imai. Cutaneous Ossifying Fibroma in a Neon Tetra ( Paracheirodon innesi ). Journal of Comparative Pathology 2016, 155, 272 -275.
AMA StyleB. Murphy, D.M. Imai. Cutaneous Ossifying Fibroma in a Neon Tetra ( Paracheirodon innesi ). Journal of Comparative Pathology. 2016; 155 (2):272-275.
Chicago/Turabian StyleB. Murphy; D.M. Imai. 2016. "Cutaneous Ossifying Fibroma in a Neon Tetra ( Paracheirodon innesi )." Journal of Comparative Pathology 155, no. 2: 272-275.
Feline immunodeficiency virus (FIV) infection results in viral persistence, a prolonged asymptomatic phase, and progressive immunopathology. During the asymptomatic phase, a cohort of experimentally FIV-infected cats exhibits features of viral latency in blood suggestive of inactive viral replication. We sought to investigate viral replication activity and genomic stability of the FIV proviral long terminal repeat (LTR) and the 5′ aspect of gag over time. FIV-infected cats during the asymptomatic phase demonstrated undetectable plasma FIV gag RNA transcripts and intermittent to undetectable blood-derived cell-associated FIV gag RNA. The LTR sequence demonstrated instability in blood-derived cells over time, in spite of low to undetectable viral replication. Sequence variation in the LTR was identified in CD4+ and CD21+ leukocytes from blood and surgically removed lymph nodes. Three single nucleotide polymorphisms (SNPs) in the LTR were commonly identified. Promoter functionality of a common LTR SNP and rare U3 mutation were examined by reporter gene assays and demonstrated either no change or increased basal FIV promoter function, respectively. In conclusion, this cohort of asymptomatic FIV-infected cats demonstrated instability of the LTR and 5’ gag sequences during the study period, in spite of undetectable plasma and rare to undetectable viral gag RNA, which suggests that blood may not accurately represent viral activity in asymptomatic FIV-infected cats.
Christina D. Eckstrand; Chadwick Hillman; Brian G. Murphy. Sequence Instability in the Proviral Long Terminal Repeat and gag Regions from Peripheral Blood and Tissue-Derived Leukocytes of FIV-Infected Cats during the Late Asymptomatic Phase. Veterinary Sciences 2016, 3, 10 .
AMA StyleChristina D. Eckstrand, Chadwick Hillman, Brian G. Murphy. Sequence Instability in the Proviral Long Terminal Repeat and gag Regions from Peripheral Blood and Tissue-Derived Leukocytes of FIV-Infected Cats during the Late Asymptomatic Phase. Veterinary Sciences. 2016; 3 (2):10.
Chicago/Turabian StyleChristina D. Eckstrand; Chadwick Hillman; Brian G. Murphy. 2016. "Sequence Instability in the Proviral Long Terminal Repeat and gag Regions from Peripheral Blood and Tissue-Derived Leukocytes of FIV-Infected Cats during the Late Asymptomatic Phase." Veterinary Sciences 3, no. 2: 10.
Chytridiomycosis, resulting from an infection with the fungal agent Batrachochytrium dendrobatidis (Bd), has resulted in widespread population declines in both wild and captive amphibians. The dwarf African frog (DAF) Hymenochirus curtipes is native to central Africa and is commonly sold throughout North America as an aquarium pet species. Here we document fatal chytridiomycosis resulting from cutaneous Bd infections in DAF purchased directly from a pet store and from a historical lethal epizootic occurring at an aquaculture facility in central California, USA, more than 25 yr ago. Histological lesions and PCR-amplified sequence data were consistent with the etiology of Bd. The potential epidemiological relevance of this infection in DAF is discussed.
Bg Murphy; C Hillman; Jm Groff. Chytridiomycosis in dwarf African frogs Hymenochirus curtipes. Diseases of Aquatic Organisms 2015, 114, 69 -75.
AMA StyleBg Murphy, C Hillman, Jm Groff. Chytridiomycosis in dwarf African frogs Hymenochirus curtipes. Diseases of Aquatic Organisms. 2015; 114 (1):69-75.
Chicago/Turabian StyleBg Murphy; C Hillman; Jm Groff. 2015. "Chytridiomycosis in dwarf African frogs Hymenochirus curtipes." Diseases of Aquatic Organisms 114, no. 1: 69-75.
Feline immunodeficiency virus (FIV) is a naturally-occurring, large animal model of lentiviral-induced immunodeficiency syndrome, and has been used as a model of HIV pathogenesis and therapeutic interventions. HIV reservoirs in the form of latent virus remain the primary roadblock to viral eradication and cure, and FIV has been previously established an animal model of lentiviral latency. The goal of this study was to determine whether administration of the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA) to aviremic, chronically FIV-infected cats would induce latent viral reactivation in vivo. A proof-of-concept experiment in a Transwell co-culture system demonstrated the ability of SAHA to reactivate latent virus which was replication competent and able to infect naïve cells. Oral SAHA (250 mg/m2) was administered with food to four asymptomatic, experimentally FIV-infected cats and one uninfected control cat, and a limited pharmacokinetic and pharmacodynamic analysis was performed. A statistically significant increase in cell-associated FIV RNA was detected in the cat with the greatest serum SAHA exposure, and cell-free viral RNA was detected at one time point in the three cats that achieved the highest levels of SAHA in serum. Interestingly, there was a significant decrease in viral DNA burden at 2 h post drug administration in the same three cats. Though the sample size is small and the drug response was modest, this study provides evidence that in vivo treatment of FIV-infected cats with the HDACi SAHA can induce viral transcriptional reactivation, which may be dependent upon the concentration of SAHA achieved in blood. Importantly, alternative putative antilatency therapy drugs, and multimodal drug combinations, could be studied in this in vivo system. The FIV/cat model provides a unique opportunity to test novel therapeutic interventions aimed at eradicating latent virus in vivo.
Samantha J. McDonnel; Molly L. Liepnieks; Brian G. Murphy. Treatment of chronically FIV-infected cats with suberoylanilide hydroxamic acid. Antiviral Research 2014, 108, 74 -78.
AMA StyleSamantha J. McDonnel, Molly L. Liepnieks, Brian G. Murphy. Treatment of chronically FIV-infected cats with suberoylanilide hydroxamic acid. Antiviral Research. 2014; 108 ():74-78.
Chicago/Turabian StyleSamantha J. McDonnel; Molly L. Liepnieks; Brian G. Murphy. 2014. "Treatment of chronically FIV-infected cats with suberoylanilide hydroxamic acid." Antiviral Research 108, no. : 74-78.
Feline immunodeficiency virus (FIV)-infected cats enter a clinically asymptomatic phase during chronic infection. Despite the lack of overt clinical disease, the asymptomatic phase is characterized by persistent immunologic impairment. In the peripheral blood obtained from cats experimentally infected with FIV-C for approximately 5 years, we identified a persistent inversion of the CD4/CD8 ratio. We cloned and sequenced the FIV-C long terminal repeat containing the viral promoter from cells infected with the inoculating virus and from in vivo-derived peripheral blood mononuclear cells and CD4 T cells isolated at multiple time points throughout the asymptomatic phase. Relative to the inoculating virus, viral sequences amplified from cells isolated from all of the infected animals demonstrated multiple single nucleotide mutations and a short deletion within the viral U3, R and U5 regions. A transcriptionally inactivating proviral mutation in the U3 promoter AP-1 site was identified at multiple time points from all of the infected animals but not within cell-associated viral RNA. In contrast, no mutations were identified within the sequence of the viral dUTPase gene amplified from PBMC isolated at approximately 5 years post-infection relative to the inoculating sequence. The possible implications of these mutations to viral pathogenesis are discussed.
B. Murphy; C. Hillman; S. McDonnel. Peripheral immunophenotype and viral promoter variants during the asymptomatic phase of feline immunodeficiency virus infection. Virus Research 2013, 179, 34 -43.
AMA StyleB. Murphy, C. Hillman, S. McDonnel. Peripheral immunophenotype and viral promoter variants during the asymptomatic phase of feline immunodeficiency virus infection. Virus Research. 2013; 179 ():34-43.
Chicago/Turabian StyleB. Murphy; C. Hillman; S. McDonnel. 2013. "Peripheral immunophenotype and viral promoter variants during the asymptomatic phase of feline immunodeficiency virus infection." Virus Research 179, no. : 34-43.
Caprine arthritis encephalitis virus (CAEV) is a lentivirus that infects both goats and sheep and is closely related to maedi-visna virus that infects sheep; collectively, these viruses are known as small ruminant lentiviruses (SRLV). Infection of goats and sheep with SRLV typically results in discrete inflammatory diseases which include arthritis, mastitis, pneumonia or encephalomyelitis. SRLV-infected animals concurrently demonstrating lentivirus-associated lesions in tissues of lung, mammary gland, joint synovium and the central nervous system are either very rare or have not been reported. Here we describe a novel CAEV promoter isolated from a sheep with multisystemic lentivirus-associated inflammatory disease including interstitial pneumonia, mastitis, polyarthritis and leukomyelitis. A single, novel SRLV promoter was cloned and sequenced from five different anatomical locations (brain stem, spinal cord, lung, mammary gland and carpal joint synovium), all of which demonstrated lesions characteristic of lentivirus associated inflammation. This SRLV promoter isolate was found to be closely related to CAEV promoters isolated from goats in northern California and other parts of the world. The promoter was denoted CAEV-ovine-MS (multisystemic disease); the stability of the transcription factor binding sites within the U3 promoter sequence are discussed.
Adeyemi O. Adedeji; Bradd Barr; Esperanza Gómez-Lucía; Brian Murphy. A Polytropic Caprine Arthritis Encephalitis Virus Promoter Isolated from Multiple Tissues from a Sheep with Multisystemic Lentivirus-Associated Inflammatory Disease. Viruses 2013, 5, 2005 -2018.
AMA StyleAdeyemi O. Adedeji, Bradd Barr, Esperanza Gómez-Lucía, Brian Murphy. A Polytropic Caprine Arthritis Encephalitis Virus Promoter Isolated from Multiple Tissues from a Sheep with Multisystemic Lentivirus-Associated Inflammatory Disease. Viruses. 2013; 5 (8):2005-2018.
Chicago/Turabian StyleAdeyemi O. Adedeji; Bradd Barr; Esperanza Gómez-Lucía; Brian Murphy. 2013. "A Polytropic Caprine Arthritis Encephalitis Virus Promoter Isolated from Multiple Tissues from a Sheep with Multisystemic Lentivirus-Associated Inflammatory Disease." Viruses 5, no. 8: 2005-2018.
Despite highly effective anti-retroviral therapy, HIV is thought to persist in patients within long-lived cellular reservoirs in the form of a transcriptionally inactive (latent) integrated provirus. Lentiviral latency has therefore come to the forefront of the discussion on the possibility of a cure for HIV infection in humans. Animal models of lentiviral latency provide an essential tool to study mechanisms of latency and therapeutic manipulation. Of the three animal models that have been described, the feline immunodeficiency virus (FIV)-infected cat is the most recent and least characterized. However, several aspects of this model make it attractive for latency research, and it may be complementary to other model systems. This article reviews what is known about FIV latency and chronic FIV infection and how it compares with that of other lentiviruses. It thereby offers a framework for the usefulness of this model in future research aimed at lentiviral eradication.
Samantha J McDonnel; Ellen E Sparger; Brian G Murphy. Feline immunodeficiency virus latency. Retrovirology 2013, 10, 1 -69.
AMA StyleSamantha J McDonnel, Ellen E Sparger, Brian G Murphy. Feline immunodeficiency virus latency. Retrovirology. 2013; 10 (1):1-69.
Chicago/Turabian StyleSamantha J McDonnel; Ellen E Sparger; Brian G Murphy. 2013. "Feline immunodeficiency virus latency." Retrovirology 10, no. 1: 1-69.
Lentiviral latency remains a principal obstacle to curative AIDS therapy. Transcriptional repression and latency permits lentiviruses to evade host immune responses and antiretroviral drugs. We have established a model of peripheral CD4+ T cell lentiviral latency in cats experimentally infected with feline immunodeficiency virus (FIV). Multiple mechanisms of lentiviral transcriptional repression have been proposed including epigenetic mechanisms resulting in promoter hypermethylation and/or chromatin condensation. Methylation of promoter-associated cytosines in the cytosine-guanine dinucleotide (CpG) has been associated with transcriptional repression in both eukaryotic promoters and integrated retroviral genomes. Using methylcytosine mapping, we examined the CpG methylation patterns in both the 5' and 3' long terminal repeats (LTR) of the FIV provirus in peripheral blood mononuclear cells, monocytes and CD4+ T cells isolated during the acute and asymptomatic phases of infection. Here we report no evidence that proviral promoter hypermethylation is associated with lentiviral latency in peripheral CD4+ T cells and monocytes obtained from experimentally FIV-infected cats.
B. Murphy; C. Hillman; M. Mok; N. Vapniarsky. Lentiviral latency in peripheral CD4+ T cells isolated from feline immunodeficiency virus-infected cats during the asymptomatic phase is not associated with hypermethylation of the proviral promoter. Virus Research 2012, 169, 117 -126.
AMA StyleB. Murphy, C. Hillman, M. Mok, N. Vapniarsky. Lentiviral latency in peripheral CD4+ T cells isolated from feline immunodeficiency virus-infected cats during the asymptomatic phase is not associated with hypermethylation of the proviral promoter. Virus Research. 2012; 169 (1):117-126.
Chicago/Turabian StyleB. Murphy; C. Hillman; M. Mok; N. Vapniarsky. 2012. "Lentiviral latency in peripheral CD4+ T cells isolated from feline immunodeficiency virus-infected cats during the asymptomatic phase is not associated with hypermethylation of the proviral promoter." Virus Research 169, no. 1: 117-126.