Sheep-associated Malignant Catarrhal Fever Research Articles

Quantification of ovine gammaherpesvirus 2 in clinical cases of cattle with sheep-associated malignant catarrhal fever.

Ovine gammaherpesvirus 2 (OvGHV2) produces sheep-associated malignant catarrhal fever (SA-MCF), a frequently lethal, lymphoproliferative disease that is characterized by widespread vascular lesions. Most studies that evaluated the viral load in tissues of animals with SA-MCF were done in the Northern Hemisphere, with scant information from the Southern part of the globe. This study investigated the viral load of OvGHV2 in the tissues of cattle and an underdeveloped fetus with SA-MCF from three distinct biomes of Brazil. All animals had clinical and histopathological manifestations consistent with SA-MCF. Molecular testing identified the OvGHV2 tegument protein and glycoprotein B genes in the tissues of all animals and the fetus. Viral quantification based on the DNA polymerase gene detected elevated loads of OvGHV2 in tissues with histopathological evidence of SA-MCF and organs with unknown histological data, except for the tissues of the fetus, where the viral load was comparatively reduced. The viral loads detected in multiple organs of cattle from this study with SA-MCF are consistent with those identified in different animal species from the USA and Europe. The detection of a low viral load of OvGHV2 in fetal tissue confirmed transplacental dissemination since elevated viral loads were detected in multiple tissues of the cow with SA-MCF. Furthermore, the elevated viral loads detected in the pulmonary tissues of cattle with interstitial pneumonia indicate that OvGHV2 is an inductor of pulmonary disease in cattle.

Molecular detection of ovine gammaherpesvirus 2 in free ranging wild boars (Sus scrofa) from Southern Brazil.

Ovine gammaherpesvirus 2 (OvGHV2) is a member of Macavirus genus, subfamily Gammaherpesvirinae, family Herpesviridae, and causes sheep associated-malignant catarrhal fever (SA-MCF) in a wide range of ungulates. However, no descriptions of SA-MCF and/or infections due to OvGHV2 were identified in the wild boar (Sus scrofa). This study investigated the occurrence of OvGHV2 in the lungs (n = 44) of asymptomatic, free ranging wild boars captured in several regions of Paraná State, Southern Brazil. A PCR assay targeting the OvGHV2 tegument protein gene amplified OvGHV2 DNA in 4.55% (2/44) of the pulmonary tissues evaluated. Sequence analysis confirmed that the OvGHV2 strains herein identified have 98.4% deducedamino acid (aa) sequence identity with the prototype strain of OvGHV2 and 96.4-100% aa identity with similar strains of OvGHV2 detected in several animal species from diverse countries. These findings confirmed that these two wild boars were infected by OvGHV2, represent the first description of this infection in these animals, and add to the number of pathogens identified in this animal species. Furthermore, these findings contrast earlier descriptions of OvGHV2 in swine since in all previous reports the infected pigs demonstrated clinical manifestations of disease. Consequently, these wild boars from Southern Brazil were subclinically infected or suffered asymptomatic infections by OvGHV2.

Sheep-associated malignant catarrhal fever in cattle: an update

Sheep-associated malignant catarrhal fever (SA-MCF) is a frequently fatal disease of many species including cattle, caused by ovine herpes virus-2. Sheep are the main reservoir host species and transmit the virus to other species, usually via aerosol. Clinical signs in affected animals can impact various body systems, and infection can be sub-clinical and become latent. No specific treatments exist, and empirical treatments are generally unrewarding. Occasionally some animals may survive, but there remains a chronic arteriopathy. Currently, the disease is controlled on farms is by reducing contact between susceptible hosts and sheep as much as possible, although a vaccine would be a useful protective strategy should one be developed.

Ovine Herpesvirus 2 Glycoprotein B Complementation Restores Infectivity to a Bovine Herpesvirus 4 gB-Null Mutant.

Ovine herpesvirus 2 (OvHV-2) and bovine herpesvirus 4 (BoHV-4) are gamma herpesviruses that belong to the genera Macavirus and Rhadinovirus, respectively. As with all herpesviruses, both OvHV-2 and BoHV-4 express glycoprotein B (gB), which plays an essential role in the infection of host cells. In that context, it has been demonstrated that a BoHV-4 gB-null mutant is unable to infect host cells. In this study, we used homologous recombination to insert OvHV-2 ORF 8, encoding gB, into the BoHV-4 gB-null mutant genome, creating a chimeric BoHV-4 virus carrying and expressing OvHV-2 gB (BoHV-4∆gB/OvHV-2-gB) that was infectious and able to replicate in vitro. We then evaluated BoHV-4∆gB/OvHV-2-gB as a potential vaccine candidate for sheep-associated malignant catarrhal fever (SA-MCF), a fatal disease of ungulates caused by OvHV-2. Using rabbits as a laboratory model for MCF, we assessed the safety, immunogenicity, and efficacy of BoHV-4∆gB/OvHV-2-gB in an immunization/challenge trial. The results showed that while BoHV-4∆gB/OvHV-2-gB was safe and induced OvHV-2 gB-specific humoral immune responses, immunization conferred only 28.5% protection upon challenge with OvHV-2. Therefore, future studies should focus on alternative strategies to express OvHV-2 proteins to develop an effective vaccine against SA-MCF.

Coding complete genome of a strain of ovine herpesvirus-2 associated with a clinical case of malignant catarrhal fever in a domestic lamb.

Ovine herpesvirus-2 causes sheep-associated malignant catarrhal fever, a fatal disease of ruminants and pigs. The virus is carried by sheep, and infection is typically subclinical. Here, we report the coding complete genome sequence of a strain of OvHV-2 obtained from a clinically affected domestic lamb.

First identification and characterization of ovine gammaherpesvirus type 2 in horses and artiodactyla from an outbreak of malignant catarrhal fever in Mexico.

Ovine gammaherpesvirus 2 (OvHV-2), a member of the genus Macavirus, causes sheep-associated malignant catarrhal fever (SA-MCF), a fatal lymphoproliferative disease affecting a wide variety of ungulates in addition to horses. This study described an outbreak of SA-MCF in Mexico and the identification of the OvHV-2 virus in primary rabbit testis cultures through the generation of intranuclear inclusion bodies, syncytia, immunofluorescence (IF), immunocytochemistry (ICC), immunohistochemistry (IHC), endpoint polymerase chain reaction (PCR), and partial sequencing of the ORF75 gene. The animals involved in this outbreak showed mucogingival ulcers in the vestibule of the mouth and tongue, hypersalivation, corneal opacity, reduced food consumption, and weight loss of variable severity. These clinical signs and the histopathological findings suggested the diagnosis of SA-MCF. Buffy coat fractions from the anticoagulated blood samples of ill animals were collected and analyzed by PCR. Positive buffy coats were used to inoculate the primary cell cultures of rabbit testis to identify the virus. Small clusters of refractile cytomegalic cells, characteristic of viral cytopathic effects, were observed between 48 and 72 h post-infection. Furthermore, intranuclear acidophilic inclusion bodies (IBs) were identified in the inoculated primary culture cells, and the cytoplasm showed immunoreactivity with hyperimmune rabbit serum against OvHV-2. Moreover, in the liver histological sections from sick deer, immunoreactive juxtanuclear IBs were identified with the same rabbit hyperimmune serum. The obtained sequences were aligned with the OvHV-2 sequences reported in GenBank and revealed a nucleotide identity higher than 98%. Based on the evidence provided in this study, we conclude that the outbreak of SA-MCF in the municipality of Tequisquiapan in the state of Queretaro, Mexico, was caused by OvHV-2. This is the second study reporting that horses are susceptible to OvHV-2 infection and can develop SA-MCF. We identified for the first time in Mexico, the presence of OvHV-2 in buffy coats from horses and Artiodactyla.

Case Reports: Clinical features and postmorteum findings of sheep-associated malignant catarrhal fever in a 2-years old bull

Malignant Catarrhal Fever (MCF) is a fatal lymphoproliferative disease of cattle and other ungulates caused by alcelaphine herpesvirus 1 (AlHV-1) and ovine herpesvirus 2 (OvHV-2), the main causative agents of wildebeest-associated MCF (WA-MCF) and sheep-associated MCF (SA-MCF), respectively. The virus is mainly spread by aerosols from pregnant or newborn sheep, goats, and wildebeest to susceptible animals. This case report presents the clinical features and post-mortem findings of an unusual case of malignant catarrhal fever (MCF) in a two-year-old bull brought to the Professor Feseha Gebreab Memorial Veterinary Teaching Hospital in Bishoftu, Ethiopia. The bull was semi-intensively managed, co-housed, and fed with sheep and other domestic animals. The animal was shivering upon arrival, with naso-ocular discharge and clouding of the eyes. The bull was febrile, with a rectal body temperature of 41.4 oC and a respiratory and heart rate of 40 and 48 beats per minute, respectively. On physical examination, the bull was emaciated, with bilateral yellowish mucopurulent naso-ocular discharge, frequent blinking, bilateral corneal opacity, salivation, a foamy mouth, head pressing, and enlargement of superficial lymph nodes. Malignant catarrhal fever was suspected based on the history and clinical signs, and empiric therapy with 10% oxytetracycline, diclofenac, and IV fluid was initiated. The bull died after receiving the third day of treatment. At necropsy, hemorrhages were found in the esophagus, trachea, and small and large intestines. In the kidney, white foci, enlargement, and fatty degeneration were observed. An ulcerated lesion was seen on the abomasum. In the gall bladder, enlargement and vascularization were also noted. The current case report confirms the rare case of clinical SA-MCF based on the history, exhibited clinical pictures, post-mortem findings, and PCR results. Separation of cattle and sheep is strongly advised to prevent SA-MCF, as no vaccine has yet been developed.

Sheep Associated-Malignant Catarrhal Fever: Past, present, and future

Members of Artiodactyla can contract the infectious disease Malignant Catarrhal Fever (MCF), which has a wide range of symptoms. Ten known viruses contribute to the disease, the two most significant ones being Ovine gamma herpes virus 2 (OvHV-2) and Alcelaphine gamma herpes virus 1 (AIHV-1). In the African subcontinent, AIHV-1 is seen in most MCF cases. In the Indian scenario, Ovine gamma herpes virus-2 is the main culprit. MCF is reported in certain pockets of India. Its threat to wildlife is not yet completely understood. In AIHV-1, wildebeests serve as the primary MCF reservoir, whereas with OvHV-2, the primary MCF reservoir is sheep. In India, OvHV-2 causes MCF in deer species, bison, and water buffaloe. The life cycle and properties of this virus are not yet wholly deciphered. To understand the impact of the disease and the threat it may pose in the future, we need to have diagnostic techniques in place. Currently, PCR is the most commonly used diagnostic technique. Work should be done on field-oriented tests like ELISA and LFA, which are helpful in areas without sophisticated lab facilities. Treatment protocols must be in place, as culling bovines is not an accepted policy in India. Probable plans for overcoming all these problems are discussed in this article.

Detection and molecular characterisation of sheep-associated malignant catarrhal fever in North Bengaluru, Karnataka

Detection and molecular characterisation of sheep-associated malignant catarrhal fever in North Bengaluru, Karnataka

A Vaccine Targeting Ovine Herpesvirus 2 Glycoprotein B Protects against Sheep-Associated Malignant Catarrhal Fever.

Malignant catarrhal fever (MCF) is a complex and often fatal disease of ungulates. Effective vaccines are needed to avoid MCF outbreaks and mitigate losses. This study aimed to evaluate a sheep-associated MCF (SA-MCF) vaccine candidate targeting ovine herpesvirus 2 (OvHV-2) glycoprotein B (gB). Rabbits were used as a laboratory animal model to test the safety, immunogenicity, and protective efficacy of a chimeric virus consisting of a recombinant, non-pathogenic strain of alcelaphine herpesvirus-1 encoding OvHV-2 ORF8 to express gB (AlHV-1∆ORF73/OvHV-2-ORF8). Viral-vectored immunizations were performed by using the AlHV-1∆ORF73/OvHV-2-ORF8 chimera alone or as a DNA prime (OvHV-2-ORF8)-virus boost regimen. The viral vector was inoculated by intravenous or intramuscular routes and the DNA was delivered by intradermal shots using a gene gun. The vaccine candidates were deemed safe as no clinical signs were observed following any of the immunizations. Anti-OvHV-2 gB antibodies with neutralizing activity were induced by all immunogens. At three weeks post-final immunization, all animals were challenged intranasally with a lethal dose of OvHV-2. MCF protection rates ranging from 66.7% to 71.4% were observed in vaccinated rabbits, while all mock-vaccinated animals developed the disease. The significant protective efficacy obtained with the vaccine platforms tested in this study encourages further trials in relevant livestock species, such as cattle and bison.

Ovine gammaherpesvirus 2 infections in cattle without typical manifestations of sheep-associated malignant catarrhal fever and concomitantly infected with bovine coronavirus.

Sheep-associated malignant catarrhal fever (SA-MCF) is a severe, frequently fatal, lymphoproliferative disease that affects a wide variety of ruminants and is caused by ovine gammaherpesvirus 2 (OvHV-2), a member of the MCF virus (MCFV) complex. The typical clinical manifestations of SA-MCF are well known and easily recognized by veterinarians, resulting in clinical diagnosis of MCF when characteristic clinical signs are present. This article describes the findings observed in cattle infected with OvHV-2 but without typical clinical manifestations of SA-MCF. Three calves with episodes of diarrhea before death and a yearling that died suddenly were investigated. Gross alterations were not suggestive of SA-MCF. Histopathology revealed a combination of proliferating vascular lesions (PVLs) and necrotizing vasculitis in three animals (two calves and the yearling); with PVLs being identified only at the carotid rete mirabile of two calves infected with OvHV-2. Additional significant histopathologic lesions included atrophic enteritis, portal lymphocytic hepatitis, interstitial pneumonia, suppurative bacterial bronchopneumonia, and pulmonary hemorrhage. An immunohistochemical assay designed to identify only antigens of MCFV revealed, positive, intralesional, intracytoplasmic immunoreactivity within epithelial cells of multiple tissues of all animals with PVLs. PCR assays amplified OvHV-2 DNA from multiple tissues of the animals that contained MCFV proteins, confirming the MCFV identified as OvHV-2. Additionally, bovine coronavirus (BCoV) nucleic acids were amplified from tissues of all animals, including the animal not infected by OvHV-2. Collectively, these findings confirmed the participation of OvHV-2 in the development of the disease patterns observed in these animals that were concomitantly infected by BCoV and provide additional confirmation that cattle can be subclinically infected with OvHV-2. Consequently, the real occurrence of OvHV-2-related disease may be more elevated than reported, since asymptomatic or subclinically infected animals are not likely to be investigated for OvHV-2. Furthermore, PVLs should be included as possible histologic indicators of OvHV-2-related diseases in ruminants.Supplementary InformationThe online version contains supplementary material available at 10.1007/s42770-021-00653-6.

Ovine gammaherpesvirus-2 infection associated with chronic interstitial pneumonia in a sheep

Sheep Associated-Malignant Catarrhal Fever (SA-MCF) is severe, frequently lethal, lymphoproliferative disease predominantly of ruminants, that is caused by ovine gammaherpesvirus-2 (OvHV-2), a member of the MCF virus (MCFV) complex. However, SA-MCF in sheep is a rare entity with few demonstrations of natural diseases worldwide. This report documents the clinical, radiographical, pathological, immunohistochemical, and molecular findings of SA-MCF in a sheep. A 4-year-old, female, mixed-breed sheep with progressive emaciation for at least one month was humanely euthanized due to poor prognosis. Clinically, the animal had tachypnea, ruminal hypomotility, productive coughing with bilateral muffling sounds during pulmonary auscultation. Radiographical evaluation revealed alveolar opacity of the cranioventral pulmonary region. Grossly, there were distinct rib impressions on the pleural surface of the lungs, suggestive of interstitial pneumonia. Histopathologic evaluation of the lungs revealed several disease patterns including 1) chronic interstitial pneumonia with vasculitis and proliferating vascular lesions, and thrombosis; 2) pulmonary abscesses associated with embolic dissemination of Corynebacterium pseudotuberculosis from superficial lymph node due to caseous lymphadenitis, CLA; 3) granulomatous pneumonia associated with pulmonary nematodes; and 4) chronic pleuritis, probably due to caseous lymphadenitis. Additional significant histologic findings included widespread lymphocytic vasculitis and proliferating vascular lesions in multiple tissues, atrophic enteritis, segmental degeneration of myocardial fibers with lymphocytic pericarditis, lymphocytic interstitial nephritis, and non-suppurative encephalitis. An immunohistochemistry (IHC) assay, based on the monoclonal antibody 15A (MAb-15A), that is specific to all MCFV known to cause MCF, revealed positive, intracytoplasmic, intralesional immunoreactivity, predominantly within bronchial and bronchiolar epithelial cells of the lungs and cryptal epithelial cells of the small intestine, followed by the renal tubular epithelium, cardiomyocytes, and with patchy immunolabelling within neurons of the cerebral cortex. Molecular testing done to detect a wide range of bacterial and viral agents of ruminant diseases, only amplified OvHV-2 DNA from fresh tissue fragments of the lungs, kidney, liver, spleen, and cerebrum. Direct sequencing confirmed that the PCR amplicon derived from the pulmonary fragments had 99.2–99.7% nucleotide sequence identity with OvHV-2 reference strains and strains of OvHV-2 from Brazil. The clinical, radiographical, gross, histopathologic, IHC, and molecular findings in the lungs are consistent with chronic interstitial pneumonia associated with infection by OvHV-2. Furthermore, the non-detection of other viral agents associated with pulmonary diseases in ruminants suggest that OvHV-2 was directly associated with the development of chronic pneumonia in this sheep. Additionally, the dental alterations, CLA, and the pulmonary nematode may have contributed towards the reduced immunological statue of the animal and facilitated the occurrence of SA-MCF. These findings may indicate that OvHV-2 may be a major participant in the pathogenesis of pulmonary disease of sheep under special conditions. Moreover, the proliferating vascular lesions identified in multiple tissues are additional evidence of chronic manifestations of OvHV-2 infections as described in chronic SA-MCF of cattle, while the widespread vasculitis is consistent with SA-MCF. Additionally, the IHC findings using the MAb-15A confirmed that this diagnostic approach is efficient to identify intralesional antigens of OvHV-2.

Cerebrocortical necrosis causes multiple deaths in Scottish ewes and lambs.

Cerebrocortical necrosis causes multiple deaths in Scottish ewes and lambs.

Molecular detection and genetic characterization of ovine gammaherpesvirus-2 (OvHV-2) in sheep in the Philippines

Abstract Ovine gammaherpesvirus-2 (OvHV-2) causes sheep-associated malignant catarrhal fever (SA-MCF) and is a fatal disease of some ruminants such as cattle, water buffalo and even-toed ungulates (such as deer, other cervids and some species of pigs). OvHV-2, however, was never reported to be present in the Philippines. Thus, this study is conducted. Out of 89 sheep blood samples from 6 farms, 58 (65.17 %) were positive for OvHV-2 using semi-Polymerase Chain Reaction targeting the tegument gene. Phylogenetic analysis suggests that the OvHV-2 sequences from sheep in the Philippines are nearly identical to the OvHV-2 sequences of animals from Brazil and Germany and 98 % identical to sequences from Turkey, India, Egypt, UK, and Mongolia. To date, this is the first report of OvHV-2 in the Philippines and could provide information in the future for the control and prevention of SA-MCF in the country.

First Molecular Evidence and Genetic Characterization of Ovine Herpesvirus 2 in Multiple Animal Species in India.

Ovine herpesvirus 2 (OvHV-2) is the causative agent of sheep-associated malignant catarrhal fever (SA-MCF), a highly fatal disease syndrome that predominantly affects susceptible hosts of the order Artiodactyla. In this study, an in-depth clinico-molecular investigation of SA-MCF disease in a morbid 50-days-old cattle calf (Bos taurus indicus) and asymptomatic infection in the in-contact reservoir hosts, sheep (Ovis aries), and goat (Capra hircus) housed on a farm located in the Southern India is reported. An OIE recommended SA-MCF type-specific PCR confirmed the etiological agent as OvHV-2. The genetic characterization and phylogenetic analyses based on the glycoprotein B (gB) gene indicate that three genetic variants of OvHV-2 had infected the animal cluster of this study. As the OvHV-2 infection eventually lead to the death of the cattle calf, and the fact that its gB sequence carried four unique amino acid substitutions (N169S, L594P, I645V, and V730A), an investigation of these substitutions impact on its stability and molecular flexibility was carried out. The mapping of these amino acid substitutions on the three-dimensional structure of gB coupled with supplementary investigations showed that these substitutions conveyed the molecular flexibility to the gB, at the cost of its stability. Future studies would be to investigate whether these gB substitutions have any impact on membrane fusion activity using a virus-free cell-to-cell membrane fusion assay. The study also highlights the importance of adopting stringent biosecurity measures where mixed animal farming is a common practice.

OvHV-2 Glycoprotein B Delivered by a Recombinant BoHV-4 Is Immunogenic and Induces Partial Protection against Sheep-Associated Malignant Catarrhal Fever in a Rabbit Model.

An efficacious vaccine for sheep-associated malignant catarrhal fever (SA-MCF) is important for the livestock industry. Research towards SA-MCF vaccine development is hindered by the absence of culture systems to propagate the causative agent, ovine herpesvirus-2 (OvHV-2), which means its genome cannot be experimentally modified to generate an attenuated vaccine strain. Alternative approaches for vaccine development are needed to deliver OvHV-2 antigens. Bovine herpesvirus 4 (BoHV-4) has been evaluated as a vaccine vector for several viral antigens with promising results. In this study, we genetically engineered BoHV-4 to express OvHV-2 glycoprotein B (gB) and evaluated its efficacy as an SA-MCF vaccine using a rabbit model. The construction of a viable recombinant virus (BoHV-4-AΔTK-OvHV-2-gB) and confirmation of OvHV-2 gB expression were performed in vitro. The immunization of rabbits with BoHV-4-AΔTK-OvHV-2-gB elicited strong humoral responses to OvHV-2 gB, including neutralizing antibodies. Following intra-nasal challenge with a lethal dose of OvHV-2, 42.9% of the OvHV-2 gB vaccinated rabbits were protected against SA-MCF, while all rabbits in the mock-vaccinated group succumbed to SA-MCF. Overall, OvHV-2 gB delivered by the recombinant BoHV-4 was immunogenic and partly protective against SA-MCF in rabbits. These are promising results towards an SA-MCF vaccine; however, improvements are needed to increase protection rates.

Detection of ovine herpesvirus-2 in clinical cases of sheep-associated malignant catarrhal fever in balinese cattle and apparently healthy sheep in East Nusa Tenggara

Malignant catarrhal fever (MCF) is a disease causing a fatal outcome in cattle and generates economic losses worldwide. This study aims to detect the cause of the disease in Balinese cattle showing clinical signs such as high fever, serous ocular mucopurulent nasal discharges, and enlargement of pre-scapularis and pre-femoralis lymphnodes. These cattle were previously housed 50 meters away from a flock of sheep which were brought from Sabu Island 3 months earlier. Samples including blood, ocular, nasal, and vaginal swabs were collected from 22 sheep, 30 goats, 33 clinically healthy cattle (22 Balinese and 11 Ongole cattle), and 3 infected Balinese cattle. Samples were processed and tested using A nested polymerase chain reaction (PCR) test. Results showed t hat 12 sheep out of 22 and 3 out of 3 infected Balinese cattle were positive MCF, suggesting a potential spread of the disease from sheep to Balinese cattle. No goats and Ongole cattle that were positive indicate that these animals are less susceptible to Ovine Herpesvirus-2 (OvHV-2) infection compared to Balinese cattle. The finding of 5 positive samples from 22 healthy Balinese cattle shows the potential of sub-clinical infection of OvHV-2.

Field Observations and Genetic Characterization of Sheep-Associated Malignant Catarrhal Fever in Egypt, 2018.

Ovine gammaherpesvirus-2 (OvHV-2) causes a lethal disease in cattle and some wild ruminants called malignant catarrhal fever (MCF), which affects the epithelial and lymphoid tissues of the respiratory and digestive tracts and has an important impact on the livestock industry. In this study, MCF was diagnosed in 18 of 427 cattle from different sites in Egypt by its typical clinical signs, found in all 18 animals: corneal opacity, fever, erosions in the buccal cavity, lymphadenitis, and purulent nasal discharge. All affected cattle had been reared in contact with clinically inconspicuous sheep. Of the 18 clinically ill cattle, 13 succumbed to the disease, resulting in estimated morbidity and case fatality rates of 4.2% and 72.2%, respectively. Five samples collected from the affected cattle were positive for OvHV-2 by real-time PCR and were used for sequencing of an 832-bp fragment of the ORF27/gp48 gene. The ORF27 nucleotide sequence of all Egyptian samples was identical, but distinct from viruses found in other parts of Africa and the Mediterranean.

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.

Detection and characterisation of sheep-associated malignant catarrhal fever infection from ruminants by using tegument and gB gene sequences of OvHV-2

In this study, positive blood and organ samples were obtained from different mixed herds of sheep and cattle against ovine herpesvirus 2 (OvHV-2) infection. Target-positive DNA was sequenced and compared with worldwide distributed OvHV-2 sequences. Tegument gene (422 base pairs) and glycoprotein B (gB) gene (2800 base pairs) amplicons of OvHV-2 genome were used for understanding of epidemiology of malignant catarrhal fever (MCF) infection in Turkey. The results of nucleotide sequencing of polymerase chain reaction (PCR) products indicated presence of sheep-associated form for MCF infection in Turkey. Although the obtained sequences were genetically different from each other, it was found that genetic variations were limited.