Bluetongue virus (Reoviridae; Orbivirus, BTV), which is usually transmitted by biting midges, affects wild and domestic ruminants worldwide, thereby causing an economically important disease. Recently, a putative new BTV strain was isolated from contaminated vaccine batches. In this study, we investigated the genomic and clinical characteristics of this isolate, provisionally designated BTV‐28. Phylogenetic analysis of BTV‐28 segment 2 (Seg‐2) showed that it is related to Seg‐2 from BTV serotypes 4, 10, 11, 17, 20 and 24, sharing 64%–66% identity in nucleotide sequences (nt) and 59%–62% in amino acid (aa) sequences of BTV VP2. BTV‐28 Seg‐6 is related to the newly reported XJ1407 BTV isolate, sharing 76.70% nt and 90.87% aa sequence identity. Seg‐5 was most closely related to a South African BTV‐4 strain, and all other segments showed close similarity to BTV‐26. Experimental infection by injection of 6‐month‐old ewes caused clinical signs in all injected animals, lasting from 2 to 3 days to several weeks post‐infection, including high body temperature, conjunctivitis, nasal discharge and rhinitis, facial oedema, oral hyperaemia, coronitis, cough, depression and tongue cyanosis. Naïve control animals, placed together with the infected sheep, displayed clinical signs and were positive for viral RNA, but their acute disease phase was shorter than that of BTV‐injected ewes. Control animals that were kept in a separated pen did not display any clinical signs and were negative for viral RNA presence throughout the experiment. Seroconversion was observed in the injected and in one of the two contact‐infected animals. These findings demonstrate that BTV‐28 infection of sheep can result in clinical manifestation, and the clinical signs detected in the contact animals suggest that it might be directly transmitted between the mammalian hosts.

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In September 2015, a large outbreak caused by epizootic hemorrhagic disease virus (EHDV) was identified in Israeli dairy and beef farms. The main clinical signs were reduced milk production, weakness, drooling, lameness and recumbency, fever, slight erythema of nasal and oral mucosae, weight loss, and abortion. Dyspnea, cachexia, and death were observed less frequently. The clinical diagnosis was confirmed by ELISAs and EHDV-specific real-time reverse transcription PCR (RT-rtPCR), followed by conventional RT-PCR of the VP2 gene and sequence analysis. According to the sequence and phylogenetic analysis of theVP2 gene, the 2015 Israeli EHD outbreak was caused by EHDV-6, which was found not only in clinically ill cattle, but also in aborted fetuses.

Summary The insect‐transmitted Shuni virus (SHUV) belongs to the Simbu serogroup of orthobunyaviruses and it is known to induce abortions, stillbirths and severe congenital malformations in ruminants and may cause neurological signs in infected horses. Here, SHUV was detected in brain samples of two Israeli cattle, which suffered from severe neurological signs that led to the deaths of the animals. During histopathological examination of the first case, a 5‐month‐old calf, small perivascular cuffs, composed mainly of neutrophils with few lymphocytes were observed in the brain stem and cerebrum. Similar infiltrates were also found to a lesser extent in the cerebellar meninges leading to the diagnosis of acute‐subacute meningoencephalitis. The histological examination of the brainstem from the second case, a 16‐month‐old heifer, revealed perivascular infiltration composed of equal numbers of macrophages and neutrophils associated with cerebral and meningeal haemorrhages. In this case encephalitis was diagnosed. Viral RNA was extracted from brain samples of both cattle that suffered from severe neurological signs and was subsequently tested by a polymerase chain reaction PCR assay specific for Simbu serogroup viruses and found positive. The presence of SHUV was subsequently confirmed by the isolation of the virus from one sample and sequence analysis of both brain samples. The comparison of the complete sequences of the coding regions of all three genome segments from both cases revealed a close relationship to Shuni viruses detected in tissue samples of aborted or malformed calves or lambs born during the last years in Israel.

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Peste-des-petits ruminants (PPR) is one of the most important infectious diseases of domesticated small ruminants. From the initial identification in 1942 in West Africa, PPR virus (PPRV) has spread throughout much of the developing world. PPRV is now considered endemic throughout Africa, with the notable exception of South Africa, the Middle-East and Israel, as well as South-, East-, and Central Asia. Despite this widespread dispersal, the evolution and transmission of PPRV in endemic populations is not well understood. This understanding will be critical in the planning of rational measures to eradicate PPRV by the planned time as defined by the FAO and OIE. To further advance the understanding of the evolution of PPRV the full genome sequence of 18 viruses isolated from Israel from consecutive years between 1997–2014 were generated. This data set is unique and crucial for the understanding of the evolution of PPRV, as it represents the first set of full-length sequence data available from consecutive years from a single geographic location. Analysis of these full genome sequences shows 96.2–99.9% nucleotide conservation across the Israel isolates and further demonstrates the strong purifying selection pressures on PPRV within Israel and globally. Four amino acid substitutions indicative of putative positive selection were additionally identified within the Israel isolates. The mean substitution rate per site per year was estimated to be 9.22 x 10−4 (95% HPD 6.206 x 10−4–1.26 x 10−3). Using Bayesian and phylogenetic analyses we further demonstrate that the PPRV isolates from Israel belongs to linage IV and form a single strong regional cluster within all other lineage IV viruses circulating worldwide implying a single incursion into Israel.

The mode and timing of virally induced cell death hold the potential of regulating viral yield, viral transmission, and the severity of virally induced disease. Orbiviruses such as the epizootic hemorrhagic disease virus (EHDV) are nonenveloped and cytolytic. To date, the death of cells infected with EHDV, the signal transduction pathways involved in this process, and the consequence of their inhibition have yet to be characterized. Here, we report that the Ibaraki strain of EHDV2 (EHDV2-IBA) induces apoptosis, autophagy, a decrease in cellular protein synthesis, the activation of c-Jun N-terminal kinase (JNK), and the phosphorylation of the JNK substrate c-Jun. The production of infectious virions decreased upon inhibition of apoptosis with the pan-caspase inhibitor Q-VD-OPH (quinolyl-valyl-O-methylaspartyl-[-2,6-difluorophenoxy]-methyl ketone), upon inhibition of autophagy with 3-methyladenine or via the knockout of the autophagy regulator Atg5, or upon treatment of infected cells with the JNK inhibitor SP600125 or the cyclin-dependent kinase (CDK) inhibitor roscovitine, which also inhibited c-Jun phosphorylation. Moreover, Q-VD-OPH, SP600125, and roscovitine partially reduced EHDV2-IBA-induced cell death, and roscovitine diminished the induction of autophagy by EHDV2-IBA. Taken together, our results imply that EHDV induces and benefits from the activation of signaling pathways involved in cell stress and death.T he epizootic hemorrhagic disease virus (EHDV) is an arbovirus (genus orbiviruses) of the Reoviridae family that is transmitted by biting midges and infects ruminants. In recent years, outbreaks of epizootic hemorrhagic disease in cattle have been reported in Israel and Turkey (1, 2), suggesting that EHDV is an emerging threat to the cattle industry in Europe (3). EHDV presents structural and sequence similarities to the better-studied bluetongue virus (BTV), sharing its repertoire of infection targets and symptoms of disease (3, 4). However, in spite of structural similarities between these viruses, a recent study suggests that preexisting immunity to BTV does not protect against EHDV infection (5). The EHDV genome is organized in 10 double-stranded RNA (dsRNA) segments encoding seven structural proteins (VP1 to VP7) and the nonstructural (NS) proteins NS1 to NS3. Recently, an additional nonstructural protein, NS4, has been identified in BTV (6, 7), raising the possibility that the same protein occurs in EHDV. The present study mainly employs the Ibaraki strain of EHDV2 (EHDV2-IBA), originally isolated from infected cattle in 1959, in Ibaraki, Japan (8). Selected experiments were also carried out with EHDV7-Israel (EHDV7-ISR), isolated from infected cattle in 2006 in Israel (1).For different types of reoviruses, including BTV, apoptosis is integral to the cellular pathogenesis they induce (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). Yet the molecular mechanisms that govern reovirus-mediated induction of apoptosis are a contentious matter (10,17,19,20). For orbiviruses in general and EHDV in partic...

During 2008–2009 in Israel, equine encephalosis virus (EEV) caused febrile outbreaks in horses. Phylogenetic analysis of segment 10 of the virus strains showed that they form a new cluster; analysis of segment 2 showed ≈92% sequence identity to EEV-3, the reference isolate. Thus, the source of this emerging EEV remains uncertain.