Immune-mediated Equine Vasculopathies.

Immune-mediated vasculopathies occur secondary to infection or another noninfectious stimulus. Potential triggers include heterologous antigens including viruses, injected proteins and drugs; or auto-antigens including immunoglobulins or other endogenous proteins. Although these conditions are rare in horses, immune-mediated vasculopathies can cause considerable morbidity, with variable clinical signs depending on severity and organ system affected. Examples include purpura hemorrhagica, systemic lupus erythematosus, drug-induced vasculitis, paraneoplastic vasculitis, and idiopathic immune-mediated vasculitis. Diagnosis is presumptive or based on histopathology of skin biopsies if cutaneous signs are present. Treatment relies on removing the inciting cause, immunosuppression, and supportive care.

Sheep-Associated Malignant Catarrhal Fever: Role of Latent Virus and Macrophages in Vasculitis.

Malignant catarrhal fever (MCF) is a sporadic, generally fatal disease caused by gammaherpesviruses in susceptible dead-end hosts. A key pathological process is systemic vasculitis in which productively infected cytotoxic T cells play a major role. Nonetheless, the pathogenesis of MCF vasculitis is not yet clear. We hypothesized that it develops due to an interaction between virus-infected cells and immune cells, and we undertook a retrospective in situ study on the rete mirabile arteries of confirmed ovine gammaherpesvirus-2 (OvHV-2)-associated MCF cases in cattle, buffalo, and bison. Our results suggest that the arteritis develops from an adventitial infiltration of inflammatory cells from the vasa vasorum, and recruitment of leukocytes from the arterial lumen that leads to a superimposed infiltration of the intima and media that can result in chronic changes including neointimal proliferation. We found macrophages and T cells to be the dominant infiltrating cells, and both could proliferate locally. Using RNA in situ hybridization and immunohistology, we showed that the process is accompanied by widespread viral infection, not only in infiltrating leukocytes but also in vascular endothelial cells, medial smooth muscle cells, and adventitial fibroblasts. Our results suggest that OvHV-2-infected T cells, monocytes, and locally proliferating macrophages contribute to the vasculitis in MCF. The initial trigger or insult that leads to leukocyte recruitment and activation is not yet known, but there is evidence that latently infected, activated endothelial cells play a role in this. Activated macrophages might then release the necessary pro-inflammatory mediators and, eventually, induce the characteristic vascular changes.

Equine pastern vasculitis in a horse associated with a multidrug-resistant Pseudomonas aeruginosa isolate.

BACKGROUND: Equine pastern vasculitis is an uncommon disorder in horses. Underlying causes are difficult to assess, especially bacterial infections. CLINICAL SUMMARY: A 13-year-old French saddle gelding horse presented for evaluation of a six weeks history of pastern dermatitis. Histopathological examination of skin biopsy samples revealed small vessel vasculitis. A pure growth of a multidrug-resistant Pseudomonas aeruginosa (MRPA) was obtained from a deep skin biopsy. Clinical remission was observed after a six week course of enrofloxacin and lesions did not recur. CONCLUSIONS AND CLINICAL IMPORTANCE: To the best of the authors' knowledge, this is the first report of a pastern vasculitis associated with MRPA and successfully treated with a six week course of enrofloxacin.

Novel Pulmonary Vasculitis with Splendore-Hoeppli Reaction in Grey Seals (Halichoerus grypus) Associated with Otostrongylus circumlitus Infection.

Lungworm infection in seals is an important cause of morbidity and mortality, inducing bronchopneumonia and affecting population dynamics in some areas of the world. We present a series of cases of lungworm infection in grey seals (Halichoerus grypus) associated with novel, significant and unusual pulmonary vascular changes. Grey seals (n = 180) that were stranded, in rehabilitation or in long-term captivity in the UK were subjected to post-mortem examination between 2012 and 2018. Lung tissue was collected from 47 individuals for histopathological examination. Polymerase chain reaction (PCR) on formalin-fixed and paraffin wax-embedded (FFPE) material was attempted for parasite identification on selected sections using lungworm-specific primers, and nematode morphology within sections was evaluated histologically. Fourteen of 47 (30%) of these grey seals showed evidence of segmental granulomatous and eosinophilic vasculitis with an intramural Splendore-Hoeppli reaction in medium to large pulmonary arteries. Intravascular nematodes suggestive of Otostrongylus circumlitus were seen in two cases. PCR on FFPE material was unable to detect a signal on selected tissue sections. Of the 14 affected seals, nine had concurrent bronchopneumonia and four had intra-alveolar/bronchiolar Parafilaroides spp. Thirteen of 14 animals with vasculitis lesions were weaned pups with only one adult affected. Previous pathological descriptions of lungworm infection in grey seals have dealt mainly with the bronchopneumonia. This case series has identified previously unrecorded vascular changes characterized by an intramural Splendore-Hoeppli reaction. Such change would impact on vascular integrity, increasing the likelihood of vascular rupture with pulmonary haemorrhage and increased risk of intravascular coagulation. A host-parasite relationship with the persistence of antigenic material following close contact with, or migration through, the blood vessel wall is suspected.

Bartonella henselae in a dog with ear tip vasculitis.

BACKGROUND: Bartonella henselae, a Gram-negative, zoonotic, alpha-proteobacteria has been previously implicated in association with cutaneous vasoproliferative lesions (bacillary angiomatosis), nodular panniculitis and multifocal erythema (erythema multiforme) in dogs. OBJECTIVE: Describe clinical, microbiological and histological lesions in a dog with ear margin vasculitis and B. henselae infection. ANIMALS: A 12-month-old, specific pathogen-free intact female beagle dog maintained in a vector-free laboratory animal resource facility. METHODS AND MATERIALS: Bartonella and Rickettsia serological evaluation, Bartonella and Rickettsia PCR, Bartonella alpha-proteobacteria growth medium (BAPGM) enrichment blood culture/PCR, histopathological investigation and confocal immunohistochemical evaluation. RESULTS: Serological investigation (seroreversion) and PCR testing of aural tissue biopsies failed to support Rickettsia rickettsii as a cause of the aural vasculitis; however, B. henselae, genotype San Antonio 2 DNA was amplified and sequenced from both ear tip margins and from normal-appearing abdominal skin. Seroconversion to B. henselae was documented retrospectively by IFA testing. Bartonella henselae organisms were visualized by confocal immunostaining within all three biopsies. Histopathology revealed small vessel necrotizing vasculitis and dermal necrosis. Bartonella henselae seroreversion and complete resolution of skin lesions occurred in conjunction with administration of oral doxycycline and enrofloxacin for six weeks. CONCLUSIONS AND CLINICAL IMPORTANCE: Bartonella henselae is an emerging zoonotic pathogen that has been associated with leucocytoclastic vasculitis in humans and may have had a contributing or causative role in the development of the cutaneous aural margin vasculitis in this beagle.

Fetal Neuropathology in Zika Virus-Infected Pregnant Female Rhesus Monkeys.

The development of interventions to prevent congenital Zika syndrome (CZS) has been limited by the lack of an established nonhuman primate model. Here we show that infection of female rhesus monkeys early in pregnancy with Zika virus (ZIKV) recapitulates many features of CZS in humans. We infected 9 pregnant monkeys with ZIKV, 6 early in pregnancy (weeks 6-7 of gestation) and 3 later in pregnancy (weeks 12-14 of gestation), and compared findings with uninfected controls. 100% (6 of 6) of monkeys infected early in pregnancy exhibited prolonged maternal viremia and fetal neuropathology, including fetal loss, smaller brain size, and histopathologic brain lesions, including microcalcifications, hemorrhage, necrosis, vasculitis, gliosis, and apoptosis of neuroprogenitor cells. High-resolution MRI demonstrated concordant lesions indicative of deep gray matter injury. We also observed spinal, ocular, and neuromuscular pathology. Our data show that vascular compromise and neuroprogenitor cell dysfunction are hallmarks of CZS pathogenesis, suggesting novel strategies to prevent and to treat this disease.

Histologic Changes Associated With Placental Separation in Gilts Infected with Porcine Reproductive and Respiratory Syndrome Virus.

The placenta is a vital organ providing the developing fetus with nutrient and gas exchange, thermoregulation, and waste elimination necessary for fetal development, as well as producing hormones to maintain pregnancy. It is hypothesized that fetal pig death in porcine reproductive and respiratory syndrome may be attributed to pathology of the maternal-fetal interface leading to premature placental separation. This study was designed to evaluate the chronologic progression of porcine reproductive and respiratory syndrome virus (PRRSV)-induced lesions at the maternal-fetal interface, with particular focus on placental separation in experimentally challenged third-trimester gilts. Fifteen gilts were inoculated with a virulent strain of PRRSV-2 on gestation day 86 ± 0.4. On multiple days postinoculation, 3 gilts along with 1 sham-inoculated control per time point were euthanized, and uterine and fetal placental tissues corresponding to each fetus were collected for histopathologic evaluation. The presence of any fetal lesion was 23 times more likely in compromised (meconium-stained and decomposed) compared with viable fetuses ( P < .001). In PRRSV-infected gilts, endometritis was more severe than placentitis, and the severity of endometrial inflammation and vasculitis increased progressively from 2 to 14 days postinoculation. Neither placental vasculitis nor a chronologic progression in the severity of placental detachment was observed. Severe placental detachment was more frequently present in PRRSV-infected compared with noninfected samples and was most significantly associated with placental inflammation, compared with other uterine lesions, viral load, or termination day. The results of this study suggest that placental separation by itself is not sufficient to significantly compromise fetal viability in reproductive porcine reproductive and respiratory syndrome.

East Coast Fever Caused by Theileria parva Is Characterized by Macrophage Activation Associated with Vasculitis and Respiratory Failure.

Respiratory failure and death in East Coast Fever (ECF), a clinical syndrome of African cattle caused by the apicomplexan parasite Theileria parva, has historically been attributed to pulmonary infiltration by infected lymphocytes. However, immunohistochemical staining of tissue from T. parva infected cattle revealed large numbers of CD3- and CD20-negative intralesional mononuclear cells. Due to this finding, we hypothesized that macrophages play an important role in Theileria parva disease pathogenesis. Data presented here demonstrates that terminal ECF in both Holstein and Boran cattle is largely due to multisystemic histiocytic responses and resultant tissue damage. Furthermore, the combination of these histologic changes with the clinical findings, including lymphadenopathy, prolonged pyrexia, multi-lineage leukopenia, and thrombocytopenia is consistent with macrophage activation syndrome. All animals that succumbed to infection exhibited lymphohistiocytic vasculitis of small to medium caliber blood and lymphatic vessels. In pulmonary, lymphoid, splenic and hepatic tissues from Holstein cattle, the majority of intralesional macrophages were positive for CD163, and often expressed large amounts of IL-17. These data define a terminal ECF pathogenesis in which parasite-driven lymphoproliferation leads to secondary systemic macrophage activation syndrome, mononuclear vasculitis, pulmonary edema, respiratory failure and death. The accompanying macrophage phenotype defined by CD163 and IL-17 is presented in the context of this pathogenesis.

Cardiac lesions in 30 dogs naturally infected with Leishmania infantum chagasi.

The hearts of 30 dogs naturally infected with Leishmania infantum chagasi were evaluated histologically and immunohistochemically. Myocardial lesions were detected in all dogs, including lymphoplasmacytic myocarditis (27/30), myonecrosis (24/30), increased interstitial collagen (22/30), lepromatous-type granulomatous myocarditis (7/30), fibrinoid vascular change (3/30), and vasculitis (1/30). The parasite was detected in the hearts of 20 of 30 dogs. The number of parasitized cells correlated with the intensity of the inflammation and with the number of granulomas. The results indicate that cardiac lesions are prevalent in dogs with naturally occurring leishmaniasis even in the absence of clinical signs of cardiac disease.

Fibroblasts express OvHV-2 capsid protein in vasculitis lesions of American bison (Bison bison) with experimental sheep-associated malignant catarrhal fever.

American bison (Bison bison) are particularly susceptible to developing fatal sheep-associated malignant catarrhal fever (SA-MCF) caused by ovine herpesvirus-2 (OvHV-2), a γ-herpesvirus in the Macavirus genus. This generally fatal disease is characterized by lymphoproliferation, vasculitis, and mucosal ulceration in American bison, domestic cattle (Bos taurus), and other clinically susceptible species which are considered non-adapted, dead-end hosts. The pathogenesis and cellular tropism of OvHV-2 infection have not been fully defined. An earlier study detected OvHV-2 open reading frame 25 (ORF25) transcripts encoding the viral major capsid protein in tissues of bison with SA-MCF, and levels of viral transcript expression positively correlated with lesion severity. To further define the cellular tropism and replication of OvHV-2 infection in vascular lesions of bison, immunofluorescence studies were performed to identify cell type(s) expressing ORF25 protein within tissues. Cytoplasmic and not nuclear ORF25 protein was demonstrated in predominantly perivascular fibroblasts in six bison with experimentally-induced SA-MCF, and there was no evidence of immunoreactivity in vascular endothelium, smooth muscle, or infiltrating leukocytes. The cytoplasmic distribution of viral major capsid protein suggests that viral replication in perivascular fibroblasts may be abortive in this dead-end host. These findings provide a novel foundation for defining the pathogenesis of vasculitis in non-adapted hosts with SA-MCF.

Circovirus in tissues of dogs with vasculitis and hemorrhage.

We characterized the complete genome of a novel dog circovirus (DogCV) from the liver of a dog with severe hemorrhagic gastroenteritis, vasculitis, and granulomatous lymphadenitis. DogCV was detected by PCR in fecal samples from 19/168 (11.3%) dogs with diarrhea and 14/204 (6.9%) healthy dogs and in blood from 19/409 (3.3%) of dogs with thrombocytopenia and neutropenia, fever of unknown origin, or past tick bite. Co-infection with other canine pathogens was detected for 13/19 (68%) DogCV-positive dogs with diarrhea. DogCV capsid proteins from different dogs varied by up to 8%. In situ hybridization and transmission electron microscopy detected DogCV in the lymph nodes and spleens of 4 dogs with vascular compromise and histiocytic inflammation. The detection of a circovirus in tissues of dogs expands the known tropism of these viruses to a second mammalian host. Our results indicate that circovirus, alone or in co-infection with other pathogens, might contribute to illness and death in dogs.

Cutaneous vasculitis in small animals.

Cutaneous vasculitis is an inflammatory process targeting blood vessels. Underlying factors include drugs, infectious diseases, adverse reactions to food, malignancies, and immune-mediated diseases. Vasculitis is a reaction pattern warranting a workup to identify triggers. Presenting symptoms include purpura, pitting edema, and skin ulcerations. Constitutional signs include fever, depression, and anorexia and seem to be present in the majority of patients. Once a diagnosis is confirmed, treatment and follow-up must be tailored to the individual. High-dose immunosuppressive medications are only recommended once infectious diseases capable of producing a similar constellation of clinical signs have been ruled out.

Presumed reactive polyarthritis and granulomatous vasculitis in a Mississippi sandhill crane (Grus canadensis pulla).

A 1.5-year-old female Mississippi sandhill crane (Grus canadensis pulla) was presented and managed for a polyarthritis of the intertarsal and tarsophalangeal articulations. Results of aerobic bacterial cultures, Mycoplasma species culture, and polymerase chain reaction testing of articular fluid did not identify any causative organisms. Results of radiographs and cytologic examination of articular fluid were consistent with an inflammatory, nonerosive polyarthritis. The arthritis did not improve with systemic anti-inflammatory and antibiotic treatment and with joint lavage. A large necrotic granulomatous mass was detected on the right shoulder area from which Staphylococcus aureus and Enterococcus species were isolated as opportunistic pathogens. Two days after surgical resection of the mass, the distal polyarthritis resolved. Histopathologic examination of the mass was consistent with granulomatous vasculitis with abscess formation of unknown origin. In this crane, the unresponsiveness to standard therapy, the presence of an infected and inflammatory mass, and the resolution of the polyarthritis after the resection of the mass strongly supported a diagnosis of reactive immune-mediated nonerosive polyarthritis. Analysis of this case suggests that immune-mediated idiopathic arthritis should be a differential diagnosis of distal polyarthritis in cranes and that an inciting source remote from the joints should be investigated in case of lack of response to standard therapy.

Molecular confirmation of ovine herpesvirus 2-induced malignant catarrhal fever lesions in cattle from Rio Grande do Norte, Brazil / Diagnóstico molecular de herpesvírus ovino tipo 2 em surto de febre catarral malígna em bovinos do Rio Grande do Norte

Molecular findings that confirmed the participation of ovine herpesvirus 2 (OVH-2) in the lesions that were consistent with those observed in malignant catarrhal fever of cattle are described. Three mixed-breed cattle from Rio Grande do Norte state demonstrated clinical manifestations that included mucopurulent nasal discharge, corneal opacity and motor incoordination. Routine necropsy examination demonstrated ulcerations and hemorrhage of the oral cavity, corneal opacity, and lymph node enlargement. Significant histopathological findings included widespread necrotizing vasculitis, non-suppurative meningoencephalitis, lymphocytic interstitial nephritis and hepatitis, and thrombosis. PCR assay performed on DNA extracted from kidney and mesenteric lymph node of one animal amplified a product of 423 base pairs corresponding to a target sequence within the ovine herpesvirus 2 (OVH-2) tegument protein gene. Direct sequencing of the PCR products, from extracted DNA of the kidney and mesenteric lymph node of one cow, amplified the partial nucleotide sequences (423 base pairs) of OVH-2 tegument protein gene. Blast analysis confirmed that these sequences have 98-100% identity with similar OVH-2 sequences deposited in GenBank. Phylogenetic analyses, based on the deduced amino acid sequences, demonstrated that the strain of OVH-2 circulating in ruminants from the Brazilian states of Rio Grande do Norte and Minas Gerais are similar to that identified in other geographical locations. These findings confirmed the active participation of OVH-2 in the classical manifestations of sheep associated malignant catarrhal fever.

Os achados moleculares confirmaram a participação do herpesvírus ovino tipo 2 (OVH-2) nas lesões observadas em um surto de febre catarral malígna em bovinos. Três bovinos oriundos de propriedade rural de Mossoró, Rio Grande do Norte apresentaram manifestações clínicas, que incluíram secreção nasal mucopurulenta, opacidade da córnea e incoordenação motora. A necropsia revelou ulcerações e hemorragias da cavidade oral, opacidade da córnea e linfonodomegalia. Os achados histopatológicos significativos incluíam vasculite necrosante generalizada, meningoencefalite não supurativa, nefrite intersticial linfocítica, hepatite linfocítica e trombose. A PCR, realizada a partir de DNA extraído do rim e do linfonodo mesentérico de um dos animais, amplificou um produto com 423 pares de base do gene da proteína do tegumento do herpesvírus ovino 2 (OVH-2). O sequenciamento direto dos produtos da PCR e a análise pelo Blast demonstraram que o produto amplificado apresentava 98-100% de identidade com sequências do OVH-2 depositadas no GenBank. As análises filogenéticas, baseadas nas sequências deduzidas de aminoácidos demonstraram que a cepa de OVH-2 circulando em ruminantes nos estados de Rio Grande do Norte e Minas Gerais são semelhantes àquelas identificadas em outras regiões geográficas. Esses achados confirmam a participação ativa de OVH-2 nas manifestações clássicas de febre catarral maligna em ovinos.

DIC and granulomatous vasculitis in a dog with disseminated histoplasmosis.

Disseminated histoplasmosis and disseminated intravascular coagulopathy were diagnosed in a 7 mo old, female spayed mixed-breed dog. The dog improved transiently with supportive care, but deteriorated shortly after initiation of antifungal therapy. The dog was subsequently euthanized. At necropsy, marked granulomatous vasculitis was identified in all affected organs. The tunicae and laminae of the arteries and arterioles were obscured by epithelioid macrophages and multinucleated giant cells admixed with necrotic material. Intracytoplasmic yeast were present within some of these macrophages. To the authors' knowledge, this is the first reported case of granulomatous vasculitis associated with Histoplasma capsulatum in a dog.

CD8(+)/perforin(+)/WC1(-) gammadelta T cells, not CD8(+) alphabeta T cells, infiltrate vasculitis lesions of American bison (Bison bison) with experimental sheep-associated malignant catarrhal fever.

Sheep-associated malignant catarrhal fever (SA-MCF) caused by ovine herpesvirus-2 (OvHV-2), a gamma-herpesvirus in the Macavirus genus, is a fatal disease associated with lymphoproliferation, lymphocytic vasculitis, and mucosal ulceration in clinically susceptible species. SA-MCF is an important threat to American bison (Bison bison) due to their high susceptibility to this disease. Currently, the pathogenesis of disease in SA-MCF is poorly understood, and the immunophenotype of lymphocytes that infiltrate the vascular lesions of bison and cattle with SA-MCF has been only partially defined. Previous single-color immunohistochemistry studies have demonstrated that CD8(+) cells and CD4(+) cells predominate within vascular infiltrates in cattle and bison. The CD8(+) cells detected in the vascular lesions of cattle and bison were assumed to be cytotoxic alphabeta T lymphocytes. However, polychromatic immunophenotyping analyses in this study showed that CD8(+)/perforin(+) gammadelta T cells, CD4(+)/perforin(-) alphabeta T cells, and B cells infiltrate vascular lesions in the urinary bladder, kidney, and liver of six bison with experimentally-induced SA-MCF. CD8(+) alphabeta T cells and WC1(+) gammadelta T cell cells were only infrequently and inconsistently identified. This study confirmed our hypothesis that the predominant CD8(+) lymphocytes infiltrating the vascular lesions of bison with SA-MCF are cytotoxic lymphocytes of the innate immune system, not CD8(+) alphabeta T cells. Results of the present study support the previous suggestions that MCF is fundamentally a disease of immune dysregulation.

Vascular lesions in pigs experimentally infected with porcine circovirus type 2 serogroup B.

Vasculitis is a hallmark lesion of the severe form of systemic porcine circovirus-associated disease (PCVAD). In 2 experimental studies with porcine circovirus type 2 serogroup b (PCV2b), 2 pigs developed fatal PCVAD with acute vasculitis, and 5 related pigs developed chronic lymphohistiocytic and plasmacytic peri- and endarteritis. Five of these pigs (1 with acute vasculitis and 4 with chronic vasculitis) had also been inoculated with bovine viral diarrhea virus type 1 (BVDV1) or BVDV1-like virus. Vascular lesions were similar, independent of whether pigs had been inoculated singly with PCV2b or dually with PCV2b and BVDV1 or BVDV1-like virus. The acute vasculitis was accompanied by marked pulmonary and mesenteric edema and pleural effusion. In situ hybridization demonstrated abundant intracytoplasmic porcine circovirus type 2 (PCV2) nucleic acid in endothelial, smooth muscle-like, and inflammatory cells within and around affected arteries. The pigs with lymphohistiocytic and plasmacytic vasculitis had lesions of systemic PCVAD, including multisystemic lymphoplasmacytic and histiocytic or granulomatous inflammation. PCV2 nucleic acid was detected in renal tubule epithelial cells, mononuclear inflammatory cells, and rare endothelial cells in noninflamed vessels in multiple tissues of these animals. The 2 pigs with acute vasculitis had no PCV2-specific antibodies (or a low titer of), whereas the pigs with lymphohistiocytic and plasmacytic vasculitis developed high antibody titers against this virus. These observations suggest that (1) acute vasculitis observed in the current studies is directly caused by PCV2b, (2) chronic vasculitis may in part be mediated by the subsequent immune response, and (3) host factors and viral strain may both contribute to vasculitis in animals infected with PCV2b.

Naturally occurring sheep-associated malignant catarrhal fever in North American pigs.

Two cases of sheep-associated malignant catarrhal fever (MCF) in pigs were diagnosed on a small farm in New York, and in Kentucky. In both cases, the initial diagnosis was based on histopathological changes representing typical lymphoproliferative vasculitis in multiple tissues of the affected pigs. Ovine herpesvirus 2 (OvHV-2) DNA was detected by polymerase chain reaction in the tissues of affected pigs in both cases. The amplified sequences were identical between the clinically affected pigs and the OvHV-2-infected sheep. Additional virological and bacteriological examination showed that the affected pigs were negative for agents that cause Aujeszky's disease, classical swine fever, porcine enterovirus, and rabies. An antibody against a conserved epitope among MCF viruses was detected in 1 clinically affected pig and 2 unaffected cohort pigs, as well as in all the associated sheep. To the authors' knowledge, this is the first report of porcine MCF in North America, and suggests that OvHV-2 is associated with clinical MCF in pigs.

Sheep-associated malignant catarrhal fever in free-ranging moose (Alces alces) in Saskatchewan, Canada.

Malignant catarrhal fever (MCF) is a sporadic disease of artiodactyls caused by several viruses in the Gammaherpesvirinae. We report two cases of MCF in free-living moose (Alces alces) from Saskatchewan. One was a thin, dehydrated, adult male found recumbent in 2006. At necropsy, ulcers were found in the intestine, bladder, and corneas. Microscopically, there was lymphocytic vasculitis and perivasculitis in many organs with infrequent fibrinoid necrosis. Ovine herpes virus-2 (OHV-2) was identified by polymerase chain reaction. A segment of the herpesviral DNA polymerase gene was 99% identical to published OHV-2 sequences. During a retrospective search of earlier cases, a female moose with lymphoplasmacytic meningoencephalitis examined in 2003 was identified and OHV-2 was amplified from paraffin-embedded tissues from this animal. We believe this to be the first description of MCF in free-ranging moose in North America. Infection requires contact with infected sheep or goats, and MCF in moose may become more prevalent as moose distribution continues to expand into agricultural prairie.