Clinical syndromes associated with the circulation of multiple serotypes of bluetongue virus in dairy cattle in Israel

Brenner, J.; Batten, Carrie; Yadin, Hagai; Bumbarov, V.; Friedgut, Orly; Rotenberg, Ditza; Golender, Natalia; Oura, C.A.L.

doi:10.1136/vr.d4629

Cited by 19 publications

(20 citation statements)

References 28 publications

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“…Bluetongue is remarkably variable in its clinical manifestations, which can range from asymptomatic infection to a lethal hemorrhagic fever ( 2 , 26 – 28 ). This variability is due to several factors related both to the infected host and the virus ( 2 , 29 – 33 ).…”

Section: Introductionmentioning

confidence: 99%

Multiple Genome Segments Determine Virulence of Bluetongue Virus Serotype 8

Janowicz

Caporale

Shaw

et al. 2015

J Virol

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Bluetongue virus (BTV) causes bluetongue, a major hemorrhagic disease of ruminants. In order to investigate the molecular determinants of BTV virulence, we used a BTV8 strain minimally passaged in tissue culture (termed BTV8L in this study) and a derivative strain passaged extensively in tissue culture (BTV8H) in in vitro and in vivo studies. BTV8L was pathogenic in both IFNAR−/− mice and in sheep, while BTV8H was attenuated in both species. To identify genetic changes which led to BTV8H attenuation, we generated 34 reassortants between BTV8L and BTV8H. We found that partial attenuation of BTV8L in IFNAR−/− mice was achieved by simply replacing genomic segment 2 (Seg2, encoding VP2) or Seg10 (encoding NS3) with the BTV8H homologous segments. Fully attenuated viruses required at least two genome segments from BTV8H, including Seg2 with either Seg1 (encoding VP1), Seg6 (encoding VP6 and NS4), or Seg10 (encoding NS3). Conversely, full reversion of virulence of BTV8H required at least five genomic segments of BTV8L. We also demonstrated that BTV8H acquired an increased affinity for glycosaminoglycan receptors during passaging in cell culture due to mutations in its VP2 protein. Replication of BTV8H was relatively poor in interferon (IFN)-competent primary ovine endothelial cells compared to replication of BTV8L, and this phenotype was determined by several viral genomic segments, including Seg4 and Seg9. This study demonstrated that multiple viral proteins contribute to BTV8 virulence. VP2 and NS3 are primary determinants of BTV pathogenesis, but VP1, VP5, VP4, VP6, and VP7 also contribute to virulence.IMPORTANCE Bluetongue is one of the major infectious diseases of ruminants, and it is listed as a notifiable disease by the World Organization for Animal Health (OIE). The clinical outcome of BTV infection varies considerably and depends on environmental and host- and virus-specific factors. Over the years, BTV serotypes/strains with various degrees of virulence (including nonpathogenic strains) have been described in different geographical locations. However, no data are available to correlate the BTV genotype to virulence. This study shows that BTV virulence is determined by different viral genomic segments. The data obtained will help to characterize thoroughly the pathogenesis of bluetongue. The possibility to determine the pathogenicity of virus isolates on the basis of their genome sequences will help in the design of control strategies that fit the risk posed by new emerging BTV strains.

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Section: Introductionmentioning

confidence: 99%

Multiple Genome Segments Determine Virulence of Bluetongue Virus Serotype 8

Janowicz

Caporale

Shaw

et al. 2015

J Virol

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“…BTV infects most ruminant species, but the clinical disease is limited to sheep and, to some extent cattle (1)(2)(3)11). Twenty-six serotypes of BTV are recognized (3,5), and the disease is endemic to many countries in Africa and Asia.…”

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confidence: 99%

Complete Genome Sequence of Bluetongue Virus Serotype 9: Implications for Serotyping

Rao¹,

Reddy

Hegde³

2012

J Virol

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bThe second complete genome of bluetongue virus serotype 9 (BTV-9) is presented in this report. The sequence analysis points to continued circulation in India of a mixed topotype virus apparently belonging to the BTV-9 serotype, and it raises questions about approaches for serotyping bluetongue viruses. Bluetongue virus (BTV) is a 10-segmented double-stranded RNA virus belonging to the genus Orbivirus, family Reoviridae. BTV infects most ruminant species, but the clinical disease is limited to sheep and, to some extent cattle (1-3, 11). Twenty-six serotypes of BTV are recognized (3,5), and the disease is endemic to many countries in Africa and Asia. Isolates from Asia appear to show more diversity, even though sequence information is available for only a few instances. In an effort to understand the diversity and molecular epidemiology for this virus, we recently reported the partial or complete genome analysis of isolates belonging to BTV serotypes 9, 10, and 21 (4, 10, 12). Here we report the complete sequence of the open reading frames of all 10 segments of a second BTV-9 virus. This virus, designated Ind-R1/07, was isolated from the southern state of Andhra Pradesh, India, in the year 2007. In contrast to whole-genome sequencing based on preamplified segments (7-10), we report here the use of next-generation sequencing (Illumina platform) to elucidate the nucleotide sequence information.The serotype of Ind-R1/07 was identified by sequencing. The size of the genome segments of BTV typically range from 822 to 3,944 bp. The 10 segments code for seven structural and five nonstructural proteins. The lengths of these proteins (in residues) in Ind-R1/07 virus are 1,302 (VP1), 955

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“…BTV-8 was detected in 2009 and 2010 in Israel and then in 2015 [38] along with a number of other BTV serotypes, which would have provided the opportunity for reassortment. In Israel, co-circulation of several BTV serotypes on the same farm has been reported previously [41], and mixed infections with two or three different BTV serotypes were identified on several occasions [38]. Therefore, it is likely that the most recent BTV-8 circulating in Israel underwent reassortment over time and now differs from its ancestor, BTV-8 ISR2008/13.…”

Section: Discussionmentioning

confidence: 99%

Origin of Bluetongue Virus Serotype 8 Outbreak in Cyprus, September 2016

Rajko-Nenow

Christodoulou²,

Thurston

et al. 2020

Viruses

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In September 2016, clinical signs, indicative of bluetongue, were observed in sheep in Cyprus. Bluetongue virus serotype 8 (BTV-8) was detected in sheep, indicating the first incursion of this serotype into Cyprus. Following virus propagation, Nextera XT DNA libraries were sequenced on the MiSeq instrument. Full-genome sequences were obtained for five isolates CYP2016/01-05 and the percent of nucleotide sequence (% nt) identity between them ranged from 99.92% to 99.95%, which corresponded to a few (2–5) amino acid changes. Based on the complete coding sequence, the Israeli ISR2008/13 (98.42–98.45%) was recognised as the closest relative to CYP2016/01-05. However, the phylogenetic reconstruction of CYP2016/01-05 revealed that the possibility of reassortment in several segments: 4, 7, 9 and 10. Based on the available sequencing data, the incursion BTV-8 into Cyprus most likely occurred from the neighbouring countries (e.g., Israel, Lebanon, Syria, or Jordan), where multiple BTV serotypes were co-circulating rather than from Europe (e.g., France) where a single BTV-8 serotype was dominant. Supporting this hypothesis, atmospheric dispersion modelling identified wind-transport events during July–September that could have allowed the introduction of BTV-8 infected midges from Lebanon, Syria or Israel coastlines into the Larnaca region of Cyprus.

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Clinical syndromes associated with the circulation of multiple serotypes of bluetongue virus in dairy cattle in Israel

Cited by 19 publications

References 28 publications

Multiple Genome Segments Determine Virulence of Bluetongue Virus Serotype 8

Multiple Genome Segments Determine Virulence of Bluetongue Virus Serotype 8

Complete Genome Sequence of Bluetongue Virus Serotype 9: Implications for Serotyping

Origin of Bluetongue Virus Serotype 8 Outbreak in Cyprus, September 2016

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