Bluetongue virus, an exceptionally potent interferon inducer in mice

Jameson, Patricia; Schoenherr, Christine; Grossberg, Sidney E.

doi:10.1128/iai.20.1.321-323.1978

Cited by 38 publications

(15 citation statements)

References 7 publications

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“…To date, limited information is available on the interplay between BTV and the host innate immune system. BTV has been recognized as a potent inducer of type I IFN in sheep [42], cattle [43] and mice [73]. However, limited data have been available on how BTV induces the IFN response of the cell and, more importantly, what counteracting measures the virus utilises to overcome this response.…”

Section: Discussionmentioning

confidence: 99%

Identification and Characterization of a Novel Non-Structural Protein of Bluetongue Virus

et al. 2011

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Bluetongue virus (BTV) is the causative agent of a major disease of livestock (bluetongue). For over two decades, it has been widely accepted that the 10 segments of the dsRNA genome of BTV encode for 7 structural and 3 non-structural proteins. The non-structural proteins (NS1, NS2, NS3/NS3a) play different key roles during the viral replication cycle. In this study we show that BTV expresses a fourth non-structural protein (that we designated NS4) encoded by an open reading frame in segment 9 overlapping the open reading frame encoding VP6. NS4 is 77–79 amino acid residues in length and highly conserved among several BTV serotypes/strains. NS4 was expressed early post-infection and localized in the nucleoli of BTV infected cells. By reverse genetics, we showed that NS4 is dispensable for BTV replication in vitro, both in mammalian and insect cells, and does not affect viral virulence in murine models of bluetongue infection. Interestingly, NS4 conferred a replication advantage to BTV-8, but not to BTV-1, in cells in an interferon (IFN)-induced antiviral state. However, the BTV-1 NS4 conferred a replication advantage both to a BTV-8 reassortant containing the entire segment 9 of BTV-1 and to a BTV-8 mutant with the NS4 identical to the homologous BTV-1 protein. Collectively, this study suggests that NS4 plays an important role in virus-host interaction and is one of the mechanisms played, at least by BTV-8, to counteract the antiviral response of the host. In addition, the distinct nucleolar localization of NS4, being expressed by a virus that replicates exclusively in the cytoplasm, offers new avenues to investigate the multiple roles played by the nucleolus in the biology of the cell.

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Section: Discussionmentioning

confidence: 99%

Identification and Characterization of a Novel Non-Structural Protein of Bluetongue Virus

et al. 2011

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“…BTV is a potent inducer of type 1 IFN in vivo and in vitro ( 5 , 21 , 63 – 66 ). IFNAR −/− mice, due to the lack of expression of the type 1 IFN receptor, are a suitable tool to study determinants of viral virulence unrelated to IFN expression ( 39 , 67 , 68 ).…”

Section: Discussionmentioning

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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“…BTV is a potent inducer of type 1 interferons (IFN-1s) including IFN-α and IFN-β (Jameson et al. 1978 ; Fulton and Pearson 1982 ; MacLachlan and Thompson 1985 ; Vitour et al. 2014 ; Saminathan et al.…”

Section: Introductionmentioning

confidence: 99%

An updated review on bluetongue virus: epidemiology, pathobiology, and advances in diagnosis and control with special reference to India

Saminathan

Singh

Khorajiya

et al. 2020

Veterinary Quarterly

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Bluetongue (BT) is an economically important, non-contagious viral disease of domestic and wild ruminants. BT is caused by BT virus (BTV) and it belongs to the genus Orbivirus and family Reoviridae. BTV is transmitted by Culicoides midges and causes clinical disease in sheep, white-tailed deer, pronghorn antelope, bighorn sheep, and subclinical manifestation in cattle, goats and camelids. BT is a World Organization for Animal Health (OIE) listed multispecies disease and causes great socio-economic losses. To date, 28 serotypes of BTV have been reported worldwide and 23 serotypes have been reported from India. Transplacental transmission (TPT) and fetal abnormalities in ruminants had been reported with cell culture adopted live-attenuated vaccine strains of BTV. However, emergence of BTV-8 in Europe during 2006, confirmed TPT of wild-type/field strains of BTV. Diagnosis of BT is more important for control of disease and to ensure BTV-free trade of animals and their products. Reverse transcription polymerase chain reaction, agar gel immunodiffusion assay and competitive enzyme-linked immunosorbent assay are found to be sensitive and OIE recommended tests for diagnosis of BTV for international trade. Control measures include mass vaccination (most effective method), serological and entomological surveillance, forming restriction zones and sentinel programs. Major hindrances with control of BT in India are the presence of multiple BTV serotypes, high density of ruminant and vector populations. A pentavalent inactivated, adjuvanted vaccine is administered currently in India to control BT. Recombinant vaccines with DIVA strategies are urgently needed to combat this disease. This review is the first to summarise the seroprevalence of BTV in India for 40 years, economic impact and pathobiology.

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Bluetongue virus, an exceptionally potent interferon inducer in mice

Abstract: The attenuated American BT-8 strain of bluetongue virus is 5 to 10 times more potent an interferon inducer than any other viral or nonviral agent reported to date, including as much as 600,000 units/ml of plasma by 8 h after intravenous injection.

Cited by 38 publications

References 7 publications

Identification and Characterization of a Novel Non-Structural Protein of Bluetongue Virus

Identification and Characterization of a Novel Non-Structural Protein of Bluetongue Virus

Multiple Genome Segments Determine Virulence of Bluetongue Virus Serotype 8

An updated review on bluetongue virus: epidemiology, pathobiology, and advances in diagnosis and control with special reference to India

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