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It is claimed that the distribution of Culicoides-borne viruses is highly influenced by climate. Equine encephalosis virus ( EEV) is a Culicoides-borne orbivirus which affects horses and was recently found to be endemic in Israel. To test whether climate is a crucial factor in the geographical distribution of EEV, we collected blood samples from horses in Israel during the years 2002, 2007 and 2010 and tested them for the abundance of antibodies to EEV. Samples were also collected in 2011 from horses that were seronegative to the virus in 2010, to determine the rate of infection with EEV. It was found that seroprevalence fluctuated between the years and that in each year it was highest in a different climatic region. Interestingly, analysis of infection rate at the different farms showed a negative association with seroprevalence at prior observations. In addition, analysis of precipitation preceding the outbreak of EEV which occurred during 2008 revealed that an extremely dry period existed several months prior to the febrile outbreak with the average precipitation of spring 2008 being significantly lower than the average spring precipitation of the years 1997-2009. It is therefore conjectured that exposure to EEV is not climate specific. Rather, it is highly influenced by herd immunity and weather fluctuations which might change annually. This finding may have important implications for the prediction of the abundance of Culicoides-borne viruses in endemic regions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article discusses the study which investigates the negative effects of sheep pox epidemic in a dairy sheep flock with regards to economic and epidemiological aspects. Accordingly, sheep pox has been known to be a contagious viral infection among sheep. As part of the investigation process, the epidemic was examined via clinical and epidemiological trials. The analysis concerning the morbidity and mortality rates, loss in milk production and the decline in milk quality has been described.

Infectious keratoconjunctivitis (IKC) is a highly contagious ocular inflammation frequently reported in domestic sheep and goats and in wild Caprinae. An unusually widespread outbreak of blindness is reported on a large dairy goat farm caused by Mycoplasma conjunctivae. Two stress factors were present prior to the onset of blindness: Firstly, Peste des Petits Ruminants (PPR) was diagnosed in several milking does three weeks prior to the first symptoms, and secondly, the entire herd was vaccinated against PPR to restrain the further propagation of the virus, which was considered a stressor for the lactating stock. Sixty-four per cent of the milking does (320/500) became temporarily or permanently blind. Subsequently, most of the stock aged 6 months or less, more than 250 kids, exhibited keratoconjunctivitis (KC). A month later clinical improvement of at least one eye was reported in 130 lactating does. [ABSTRACT FROM AUTHOR]

Infectious agents including viruses are important abortifacients and can cause fetal abnormalities in livestock animals. Here, samples that had been collected in Israel from aborted or malformed ruminant fetuses between 2015 and 2019 were investigated for the presence of the following viruses: the reoviruses bluetongue virus (BTV) and epizootic hemorrhagic disease virus (EHDV), the flaviviruses bovine viral diarrhea virus (BVDV) and border disease virus (BDV), the peribunyaviruses Shuni virus (SHUV) and Akabane virus (AKAV), bovine herpesvirus type 1 (BoHV-1) and bovine ephemeral fever virus (BEFV). Domestic (cattle, sheep, goat) and wild/zoo ruminants were included in the study. The presence of viral nucleic acid or antigen could be confirmed in 21.8 % of abnormal pregnancies (213 out of 976 investigated cases), with peribunyaviruses, reoviruses and pestiviruses being the most prevalent. At least four different BTV serotypes were involved in abnormal courses of pregnancy in Israel. The subtyping of pestiviruses revealed the presence of two BDV and several distinct BVDV type 1 strains. The peribunyaviruses AKAV and SHUV were identified annually throughout the study period, however, variation in the extent of virus circulation could be observed between the years. In 2018, AKAV even represented the most detected pathogen in cases of small domestic ruminant gestation abnormalities. In conclusion, it was shown that various viruses are involved in abnormal courses of pregnancy in ruminants in Israel.

Outbreaks of the European Bluetongue virus (BTV) serotype 8 (BTV-8), which are characterized by activity cycles separated by years of inactivity, may be influenced by genetic changes of the virus or by herd immunity. BTV activity in Israel is characterized by similar dynamics, but differs from European countries in its vector population, environmental conditions, and lack of cattle vaccination against this serotype. Comparison of these two geographical systems and characterization of their epidemiological connection is therefore of high interest in-order to better understand the factors influencing BTV-8 evolution. BTV-8, closely related to the European strain, was introduced to Israel in 2008. It was at the center of BT outbreaks in 2010 and 2015-2016 and thereafter was lastly isolated in Israel in 2019. We performed genetic analyses of twelve BTV-8 Israeli strains isolated between 2008 and 2019 and compared them with published sequences of BTV-8 isolated in other countries. The analysis revealed a single introduction of BTV-8 into Israel and thereafter extensive occurrence of genomic drifts and multiple reassortments with local BTV strains. Comparison of the Israeli and Cypriot BTV-8 from 2015 to 2016 suggests transmission of the virus between the two countries and a separate and parallel development from European or other Israeli BTV-8 strains. The parallel development of other BTV-8 strains was demonstrated by the identification of the Israeli BTV-8 ISR-1194/1/19 strain, which exhibited common origin with reassorted Israeli BTV-8 strains from 2010 and additional reassortment of seven segments. In order to reveal the source of BTV-8 introduction into Israel we performed BEAST analysis which showed that a probable common ancestor for both European and Israeli BTV-8 presumably existed in 2003-2004. In 2019, a possible new introduction occurred in Israel, where a novel BTV-8 strain was detected, sharing ~95% identity by segments 2 and 6 with Nigerian BTV-8NIG1982/07 and European-Middle Eastern strains. The results of the study indicate that Israel and neighboring countries consist a separate environmental and evolutionary system, distinct from European ones.

Shuni virus (SHUV), an insect-transmitted orthobunyavirus of the Simbu serogroup within the family Peribunyaviridae, may induce severe congenital malformations when naïve ruminants are infected during gestation. Only recently, another clinical presentation in cattle, namely neurological disease after postnatal infection, was reported. To characterize the course of the disease under experimental conditions and to confirm a causal relationship between the virus and the neurological disorders observed in the field, six calves each were experimentally inoculated (subcutaneously) with two different SHUV strains from both clinical presentations, that is encephalitis and congenital malformation, respectively. Subsequently, the animals were monitored clinically, virologically and serologically for three weeks. All animals inoculated with the 'encephalitis strain' SHUV 2162/16 developed viremia for three to four consecutive days, seroconverted, and five out of six animals showed elevated body temperature for up to three days. No further clinical signs such as neurological symptoms were observed in any of these animals. However, four out of six animals developed a non-suppurative meningoencephalitis, characterized by perivascular cuffing and glial nodule formation. Moreover, SHUV genome could be visualized in brain tissues of the infected animals by in situ hybridization. In contrast to the 'encephalitis SHUV strain', in animals subcutaneously inoculated with the strain isolated from a malformed newborn (SHUV 2504/3/14), which expressed a truncated non-structural protein NSs, a major virulence factor, no viremia or seroconversion, was observed, demonstrating an expected severe replication defect of this strain in vivo. The lack of viremia further indicates that virus variants evolving in malformed foetuses may represent attenuated artefacts as has been described for closely related viruses. As the neuropathogenicity of SHUV could be demonstrated under experimental conditions, this virus should be included in differential diagnosis for encephalitis in ruminants, and cattle represent a suitable animal model to study the pathogenesis of SHUV., (© 2020 The Authors. Transboundary and Emerging Diseases published by Wiley-VCH GmbH.)

An Egyptian fruit bat (Rousettus aegyptiacus) from the Zoological Gardens, at Tel Aviv, Israel, showed pox-like clinical signs including vesicular and nodular skin lesions on the wings. Cell culture isolation, histopathology, electron microscopy and molecular analysis, revealed the presence of a novel bat poxvirus. Future research is needed to determine whether this virus can affect human health., (© 2020 Kimron Veterinary Institute. Veterinary Medicine and Science Published by John Wiley & Sons Ltd.)

In this paper, the results of the diagnostic activities on Bluetongue virus serotype 3 (BTV-3) conducted at Kimron Veterinary Institute (Beit Dagan, Israel) between 2013 and 2018 are reported. Bluetongue virus is the causative agent of bluetongue (BT), a disease of ruminants, mostly transmitted by competent Culicoides species. In Israel, BTV-3 circulation was first detected in 2013 from a sheep showing classical BT clinical signs. It was also evidenced in 2016, and, since then, it has been regularly detected in Israeli livestock. Between 2013 and 2017, BTV-3 outbreaks were limited in sheep flocks located in the southern area only. In 2018, BTV-3 was instead found in the Israeli coastal area being one of the dominant BTV serotypes isolated from symptomatic sheep, cattle and goats. In Israeli sheep, BTV-3 was able to cause BT classical clinical manifestations and fatalities, while in cattle and goats infection ranged from asymptomatic forms to death cases, depending on either general welfare of the herds or on the occurrence of viral and bacterial co-infections. Three different BTV-3 strains were identified in Israel between 2013 and 2018: ISR-2019/13 isolated in 2013, ISR-2153/16 and ISR-2262/2/16 isolated in 2016. Sequencing and phylogenetic analysis of these strains showed more than 99% identity by segment (Seg) 2, 5, 6, 7, and 8 sequences. In contrast, a wide range of diversity among these strains was exhibited in other viral gene segments, implying the occurrence of genome reassortment between these local circulating strains and those originating from Africa. The genome sequences of the BTV-3 isolated in 2017 and 2018 were most closely related to those of the ISR-2153/16 strain suggesting their common ancestor. Comparison of BTV-3 Israeli strains with those recently detected in the Mediterranean region uncovered high percentage identity (98.19-98.28%) only between Seg-2 of all Israeli strains and the BTV-3 Zarzis/TUN2016 strain. A 98.93% identity was also observed between Seg-4 sequences of ISR-2019/13 and the BTV-3 Zarzis/TUN2016 strain. This study demonstrated that BTV-3 has been circulating in the Mediterranean region at least since 2013, but, unlike the other Mediterranean strains, Israeli BTV-3 were able to cause clinical signs also in cattle., (Copyright © 2020 Golender, Bumbarov, Eldar, Lorusso, Kenigswald, Varsano, David, Schainin, Dagoni, Gur, Kaplan, Gorohov, Koren, Oron, Khinich, Sclamovich, Meir and Savini.)

The full genome sequences of two isolates of bluetongue virus (BTV) from a commercial sheeppox vaccine were determined. Strain SPvvvv/02 shows low sequence identity to its closest relative, strain BTV-26 KUW2010/02, indicating the probable detection of a novel BTV genotype, whereas strain SPvvvv/03 shows high sequence identity to strain BTV-28/1537/14., (Copyright © 2020 Rajko-Nenow et al.)

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., (© 2019 Blackwell Verlag GmbH.)

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., (© 2019 Blackwell Verlag GmbH.)

Simbu serogroup viruses induce acute clinical diseases and abnormal courses of pregnancies in livestock. In Israel, two members of this serogroup, namely Akabane virus (AKAV) and Shuni virus (SHUV), were recently detected and, in Europe, Schmallenberg virus (SBV) poses a threat to ruminants. To address this emerging problem, a universal S-segment-based real-time RT-PCR assay (Uni-S) for the detection of Simbu serogroup viruses was established, which, additionally, enabled species identification of the detected viruses by subsequent sequencing. The newly developed probe-based PCR system enabled reliable detection of a comprehensive panel of Simbu viruses. Furthermore, several SBV isolates and German field samples were tested by the new Uni-S system in comparison to a SBV-specific real-time RT-PCR and both assays exhibited equally high levels of sensitivities. Finally, co-circulation of AKAV and SHUV in Israel was confirmed by analyzing field samples using the Uni-S assay followed by sequence analysis of the positive samples. To validate the test specificity, blood and tissue samples from animals negative for Simbu viruses, preparations of genetically related viruses and additional ruminant pathogens were examined and all were found to be negative. In conclusion, the new assay enabled sensitive and rapid universal molecular detection of Simbu viruses and is expected to serve as a valuable method for infection diagnosis, especially in regions where several Simbu serogroup members circulate., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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.

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.

Shuni virus (SHUV) was recently identified in Israel in several brains of ovine, bovine, and goat fetuses and newborn animals with congenital arthrogryposis-hydranencephaly syndrome. In the present study, the sequences of several Israeli SHUV strains were analyzed in detail; based on the small genome segment which encodes the nucleocapsid protein and the small nonstructural protein (NSs), a very high similarity of 99-100 % among each other was found. In contrast to the highly conserved N protein, several mutations were found within the NSs-coding sequence of SHUVs present in brain samples of malformed fetuses, resulting in a considerably frequent appearance of stop codons. Interferon alpha/beta production was demonstrated in an in-vitro interferon bioassay; hence, the virus isolated from the brain of a malformed sheep fetus acquired mutations, resulting in the loss of its NSs protein function.

Bluetongue (BT), an arthropod-borne viral disease of ruminants, a ects sheep most severely than other domestic animals. Bluetongue virus serotype 24 (BTV-24) is one of 26 known Bluetongue virus (BTV) serotypes. In this article, we present data of phylogenetic analysis of 9 viral genes (Seg1, Seg2, Seg3, Seg4, Seg5, Seg6, Seg8, Seg9, and Seg10) from 8 Israeli BTV-24 isolates and relate the genotype of the BTV-24 isolates to their phenotype with regard to clinical manifestations. The high level of genetic identity (> 99.6%) between Seg2, Seg4 and Seg5 in all 8 BTV-24 isolates indicated that these segments shared the same viral ancestor. Phylogenetic analysis of Seg1, Seg3, Seg5, Seg8, Seg9, and Seg10 revealed that the Israeli BTV-24 strains comprised 4 variants. Five of the viruses revealed high identity among all 9 segments, and represented variant 1. A second variant (BTV24/3027/6/10), isolated in 2010, showed signi cant variation from variant 1 in 3 gene segments (VP-1, VP-3, and NS-3 genes). A third variant (BTV24/3027/1/10) showed signi cant variation from variant 1 in 6 segments (VP-1, VP-3, VP-6 and NS-1, NS-2 and NS-3 genes), while a fourth variant (BTV24/2214/1/10) showed signi cant variation from variant 1 in 4 segments (VP-1, NS-1, NS-2 and NS-3 genes). These marked di erences in sequence identity indicate that a high level of genetic reassortment is occurring between co-circulating BTV strains in Israel.

Orbiviruses, some of which are virulent in ruminant species, are transmitted by blood- sucking insects. They can cause the smallest blood vessels to leak, leading to oedema, which is presented as Bluetongue (BT) and/or Epizootic haemorrhagic diseases (EHD). Other clinical manifestations include big-muscle necrosis, excessive scialorrea, and coronitis. Pathology and laboratory testing can con rm the involvement of orbivirus. Bluetongue infection in naïve sheep can elicit the 'classical signs' of the disease and, therefore, can warn of Bluetongue virus' (BTV) attacks and of increased vector activity. In 2006, infection of cattle by serotype 7 of the Epizootic haemorrhagic disease virus (EHDV) was detected in Israel, with lesions clinically identical to those of BT disease in sheep. In 2006, serotype 15 of the BTV (BTV-15) was isolated in Israel from sheep with acute BT. In 2008 clinical BT in cattle was reported and con rmed in Israel. To date, additional serotypes (BTV-2, BTV-4, BTV-5, BTV-8, BTV-12, BTV-16, and BTV-24) have been reported, of these BTV-5, BTV-8, BTV-12, and BTV-24 were isolated for the rst time in the region. Some of these serotypes have been detected in animals with simultaneous double/triple infections with di erent BTV serotypes, so that reassortment may also occur during these simultaneous infections. The use of local strains for the development of inactivated or subunit vaccines would however help to ensure antigenic matching. Various changes in orbiviral diseases occurred between 2006 and 2013 in Israel, and similarities and di erences between Israel and Europe have been reported in this study.

In this report we describe the detection and identification of Bluetongue virus (BTV) contaminations in commercial vaccines. BTV RNA was detected in vaccine batches of Lumpy skin disease (LSD) and Sheep pox (SP) using quantitative PCR (qPCR) for VP1 and NS3 genes. Both batches were positive for VP1 and NS3 in qPCR. The LSD vaccine-derived sample was positive for VP1 and VP2 in conventional PCR. The SP vaccine-derived sample was examined by amplification of VP1, VP4, VP6, VP7, NS2 and NS3 gene segments in conventional PCR. The SP vaccine-derived sample was further propagated in embryonated chicken eggs (ECE) and Vero cells. Preliminary sequence analysis showed that the LSD vaccine-derived sequence was 98-99% similar to BTV9. Analysis of the six genomic segments from the SP vaccine-derived isolate showed the highest similarity to BTV26 (66.3-97.8%). These findings are particularly important due to the effect of BTV on cattle and sheep, for which the vaccines are intended. They also demonstrate the necessity of rigorous vaccine inspection and strict vaccine production control., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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.