Expression profiling of the host and the Ovine Herpesvirus 2 pathogen during malignant catarrhal fever of cattle
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ABSTRACT:
ORGANISM(S): Ovine gammaherpesvirus 2 Bos taurus
PROVIDER: GSE13854 | GEO | 2009/08/01
SECONDARY ACCESSION(S): PRJNA110535
REPOSITORIES: GEO
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Project description:This SuperSeries is composed of the following subset Series: GSE13852: Expression profiling of Bos taurus lymph nodes upon infection with Ovine Herpesvirus 2 GSE13853: Expression profiling of Ovine Herpesvirus 2-infected lymph nodes from Bos taurus Refer to individual Series
2010-05-15 | E-GEOD-13854 | biostudies-arrayexpress
Project description:BackgroundMalignant catarrhal fever (MCF) is a lethal disease of cattle, characterized by vasculitis, necrosis, and accumulation of activated, dysregulated cytotoxic lymphocytes in various tissues. Ovine gamma herpesvirus 2 (OvHV-2) is a causative agent of MCF, which may trigger the disease through immunopathogenic pathways. Lymphocytes are the main target of the virus. However, the pathogenic basis of the disease is still mysterious.Methods/findingsWe hypothesized that the gene expression patterns of OvHV-2 and the relative abundances of host cell transcripts in lymphnodes may be used to identify pathways that help to explain the pathogenesis of MCF. Therefore, viral and host cell gene expression patterns in lymph nodes of animals with MCF and healthy controls were analyzed by microarray. Two regions on the viral genome were transcriptionally active, one encoding an orthologue to the latency-associated nuclear antigen (ORF73) of other gamma herpesviruses, the other with no predicted open reading frame. A vast number of transcripts related to inflammatory processes, lymphocyte activation, cell proliferation and apoptosis were detected at different abundances. However, the IL-2 transcript was eminent among the transcripts, which were, compared to healthy controls, less abundant in animals with MCF. The ratio between CD4- and CD8-positive T-lymphocytes was decreased in the lymphnodes of animals with MCF compared to healthy controls. In contrast, the same ratio was stable, when peripheral blood lymphocytes were analyzed.Conclusions/significanceThe phenotype of mice with a deficient IL-2-system almost perfectly matches the clinical signs observed in cattle with MCF, which feature a significantly decreased IL-2 transcript abundance, compared to healthy cattle. This supports the hypothesis that immunopathogenic events are linked to the pathogenesis of MCF. IL-2-deficiency may play an important role in the process. Therefore, this work opens new avenues for research on MCF.
| S-EPMC2705673 | biostudies-literature
Project description:IntroductionMalignant catarrhal fever (MCF) is a rare, under-explored lethal viral infection of cattle with gammaherpesvirus aetiological agents. Most often, the disease occurs on farms where cattle and sheep are kept together. However, other trigger mechanisms and environmental factors contribute. This study investigates the causation of MCF.Material and methodsAn outbreak of MCF occurred in June - August 2017 in Kharchev village in Irkutsk Oblast, Russia. In this paper, we provide epidemiological (sanitary status of pastures, watering places, and premises) and weather data during the outbreak, and descriptions of the clinical signs and post-mortem changes in cattle. The virus was detected and isolated from pathological material samples and identified by molecular methods.ResultsExtreme weather conditions, mixed-herd cattle and sheep farming, and unsatisfactory feed quality contributed to the outbreak. A virus related to herpesvirus OvHV2 was isolated and typed (MCF/Irkutsk/2017). Phylogenetic analysis showed its close genetic relationship to isolates from cattle and sheep in Germany, USA, and the Netherlands.ConclusionSporadic outbreaks of MCF caused by biotic and abiotic factors together are typical for the Russian Federation, and the Irkutsk outbreak epitomised this. Temperature anomalies caused pasture depletion, resulting in feed and water deficiency for grazing animals and dehydration and acidosis. Heat stress in animals ultimately led to the occurrence of MCF in the herd.
| S-EPMC7305638 | biostudies-literature
Project description:Protection of cattle from alcelaphine herpesvirus-1 (AlHV-1)-induced malignant catarrhal fever (MCF) has been described previously, using an attenuated virus vaccine in an unlicensed adjuvant. The vaccine was hypothesised to induce a protective barrier of virus-neutralising antibody in the oro-nasal region, supported by the observation of high titre neutralising antibodies in nasal secretions of protected animals. Here we describe further analysis of this vaccine strategy, studying the effectiveness of the vaccine formulated with a licensed adjuvant; the duration of immunity induced; and the virus-specific antibody responses in plasma and nasal secretions. The results presented here show that the attenuated AlHV-1 vaccine in a licensed adjuvant protected cattle from fatal intranasal challenge with pathogenic AlHV-1 at three or six months. In addition, animals protected from MCF had significantly higher initial anti-viral antibody titres than animals that succumbed to disease; and these antibody titres remained relatively stable after challenge, while titres in vaccinated animals with MCF increased significantly prior to the onset of clinical disease. These data support the view that a mucosal barrier of neutralising antibody blocks infection of vaccinated animals and suggests that the magnitude of the initial response may correlate with long-term protection. Interestingly, the high titre virus-neutralising antibody responses seen in animals that succumbed to MCF after vaccination were not protective.
| S-EPMC3425131 | biostudies-other
Project description: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 Information The online version contains supplementary material available at 10.1007/s42770-021-00653-6.
| S-EPMC8590972 | biostudies-literature
Project description:Malignant catarrhal fever (MCF) was diagnosed by clinical signs and lesions in five out of six white-tailed deer (Odocoileus virginianus) in a North American zoo. The clinical signs and histopathological lesions in these deer were typical of MCF. Antibody to an epitope conserved among the MCF viruses was detected in the sera collected from the deer. PCR failed to amplify viral sequences from DNA extracted from peripheral blood leukocytes (PBL) and/or spleens of the deer with primers specific for ovine herpesvirus 2 (OHV-2) or specific for alcelaphine herpesvirus 1 (AHV-1). By using degenerate primers targeting a conserved region of a herpesviral DNA polymerase gene, a DNA fragment was amplified from the PBL or spleens of all six deer and sequenced. Alignment of the sequences demonstrated that the virus in the deer belongs to the Gammaherpesvirinae subfamily, exhibiting 82% identity to OHV-2, 71% to AHV-1, and 60% to a newly identified bovine lymphotropic herpesvirus. This virus, which causes classical MCF in white-tailed deer, is a newly recognized agent belonging to the MCF group of gammaherpesviruses. It is the third reported pathogenic MCF virus, genetically distinct but closely related to OHV-2 and AHV-1. The reservoir for the virus has not been identified.
| S-EPMC86438 | biostudies-literature
Project description:Alcelaphine herpesvirus 1 (AlHV-1) is a ?-herpesvirus (?-HV) carried asymptomatically by wildebeest. Upon cross-species transmission, AlHV-1 induces an acute and fatal lymphoproliferative disease named malignant catarrhal fever (MCF) in many ruminants, including cattle and the rabbit model. Latency has been shown to be essential for MCF induction. However, the mechanisms causing the activation and proliferation of infected CD8+ T cells are unknown. Many ?-HVs express microRNAs (miRNAs). These small noncoding RNAs can suppress host or viral target genes involved in various pathways and are thought to facilitate viral infection and/or mediate activation and proliferation of infected lymphocytes. AlHV-1 genome has been predicted to encode a large number of miRNAs. However, their precise contribution in viral infection and pathogenesis in vivo remains unknown. Here, we have cloned small RNAs and sequenced 36 potential miRNAs expressed in a lymphoblastoid cell line propagated from a calf infected with AlHV-1 and developing MCF. Among the sequenced candidate miRNAs, 32 were expressed on the reverse strand of the genome in two main clusters. The expression of these 32 viral miRNAs was further validated using Northern blot and qRT-PCR in lymphoid organs of MCF-developing calves or rabbits. To determine the concerted contribution in MCF of 28 viral miRNAs clustered in the non-protein-coding region of the AlHV-1 genome, a recombinant virus was produced. The absence of these 28 miRNAs did not affect viral growth in vitro nor MCF induction in rabbits, demonstrating that AlHV-1 miRNAs clustered in the non-protein-coding genomic region are not essential for MCF induction. Small RNA sequencing from total RNA from AlHV-1-infected bovine lymphoblastoid cell line propagated with interleukin 2
2015-08-27 | E-GEOD-71056 | biostudies-arrayexpress
Project description:Alcelaphine herpesvirus 1 (AlHV-1) is a γ-herpesvirus (γ-HV) carried asymptomatically by wildebeest. Upon cross-species transmission, AlHV-1 induces an acute and fatal lymphoproliferative disease named malignant catarrhal fever (MCF) in many ruminants, including cattle and the rabbit model. Latency has been shown to be essential for MCF induction. However, the mechanisms causing the activation and proliferation of infected CD8+ T cells are unknown. Many γ-HVs express microRNAs (miRNAs). These small noncoding RNAs can suppress host or viral target genes involved in various pathways and are thought to facilitate viral infection and/or mediate activation and proliferation of infected lymphocytes. AlHV-1 genome has been predicted to encode a large number of miRNAs. However, their precise contribution in viral infection and pathogenesis in vivo remains unknown. Here, we have cloned small RNAs and sequenced 36 potential miRNAs expressed in a lymphoblastoid cell line propagated from a calf infected with AlHV-1 and developing MCF. Among the sequenced candidate miRNAs, 32 were expressed on the reverse strand of the genome in two main clusters. The expression of these 32 viral miRNAs was further validated using Northern blot and qRT-PCR in lymphoid organs of MCF-developing calves or rabbits. To determine the concerted contribution in MCF of 28 viral miRNAs clustered in the non-protein-coding region of the AlHV-1 genome, a recombinant virus was produced. The absence of these 28 miRNAs did not affect viral growth in vitro nor MCF induction in rabbits, demonstrating that AlHV-1 miRNAs clustered in the non-protein-coding genomic region are not essential for MCF induction.
2015-08-27 | GSE71056 | GEO
Project description:BACKGROUND:Wildebeest associated malignant catarrhal fever (WA-MCF) is a fatal disease of cattle. Outbreaks are seasonal and associated with close interaction between cattle and calving wildebeest. In Kenya, WA-MCF has a dramatic effect on cattle-keepers who lose up to 10% of their cattle herds per year. The objective of this study was to report the impact of WA-MCF on a commercial ranch and assess the performance of clinical diagnosis compared to laboratory diagnosis as a disease management tool. A retrospective study of WA-MCF in cattle was conducted from 2014 to 2016 at Kapiti Plains Ranch Ltd., Kenya. During this period, 325 animals showed clinical signs of WA-MCF and of these, 123 were opportunistically sampled. In addition, 51 clinically healthy animals were sampled. Nested polymerase chain reaction (PCR) and indirect enzyme linked immunosorbent assay (ELISA) were used to confirm clinically diagnosed cases of WA-MCF. A latent class model (LCM) was used to evaluate the diagnostic parameters of clinical diagnosis and the tests in the absence of a gold standard. RESULTS:By PCR, 94% (95% C.I. 89-97%) of clinically affected animals were positive to WA-MCF while 63% (95% C.I. 54-71%) were positive by indirect ELISA. The LCM demonstrated the indirect ELISA had poor sensitivity 63.3% (95% PCI 54.4-71.7%) and specificity 62.6% (95% PCI 39.2-84.9%) while the nested PCR performed better with sensitivity 96.1% (95% PCI 90.7-99.7%) and specificity 92.9% (95% PCI 76.1-99.8%). The sensitivity and specificity of clinical diagnosis were 99.1% (95% PCI 96.8-100.0%) and 71.5% (95% PCI 48.0-97.2%) respectively. CONCLUSIONS:Clinical diagnosis was demonstrated to be an effective method to identify affected animals although animals may be incorrectly classified resulting in financial loss. The study revealed indirect ELISA as a poor test and nested PCR to be a more appropriate confirmatory test for diagnosing acute WA-MCF. However, the logistics of PCR make it unsuitable for field diagnosis of WA-MCF. The future of WA-MCF diagnosis should be aimed at development of penside techniques, which will allow for fast detection in the field.
| S-EPMC6396541 | biostudies-literature
Project description:Malignant catarrhal fever (MCF) is a fatal lymphoproliferative disease of cattle that, in East Africa, results from transmission of the causative virus, alcelaphine herpesvirus 1 (AlHV-1), from wildebeest. A vaccine field trial involving an attenuated AlHV-1 virus vaccine was performed over two wildebeest calving seasons on the Simanjiro Plain of northern Tanzania. Each of the two phases of the field trial consisted of groups of 50 vaccinated and unvaccinated cattle, which were subsequently exposed to AlHV-1 challenge by herding toward wildebeest. Vaccination resulted in the induction of virus-specific and virus-neutralizing antibodies. Some cattle in the unvaccinated groups also developed virus-specific antibody responses but only after the start of the challenge phase of the trial. PCR of DNA from blood samples detected AlHV-1 infection in both groups of cattle but the frequency of infection was significantly lower in the vaccinated groups. Some infected animals showed clinical signs suggestive of MCF but few animals went on to develop fatal MCF, with similar numbers in vaccinated and unvaccinated groups. This study demonstrated a baseline level of MCF-seropositivity among cattle in northern Tanzania of 1% and showed that AlHV-1 virus-neutralizing antibodies could be induced in Tanzanian zebu shorthorn cross cattle by our attenuated vaccine, a correlate of protection in previous experimental trials. The vaccine reduced infection rates by 56% in cattle exposed to wildebeest but protection from fatal MCF could not be determined due to the low number of fatal cases.
| S-EPMC4742522 | biostudies-literature