Conformation of the VP2 protein of bluetongue virus (BTV) determines the involvement in virus neutralization of highly conserved epitopes within the BTV serogroup

White, John R.; Eaton, Bryan T.

doi:10.1099/0022-1317-71-6-1325

Cited by 43 publications

(19 citation statements)

References 19 publications

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“…Despite numerous studies which demonstrate the VP2 gene of BTV to be serotype-specific and the most variable gene between serotypes (Fukusho et al, 1987;Huismans & Cloete, 1987;Mertens et al, 1987;Gould, 1988;Ritter & Roy, 1988;Yamaguchi et al, 1988;Heidner et al, 1991), this and earlier studies confirm that epitopes may be conserved between serotypes in a neutralizing or non-neutralizing conformation (Ristow et al, 1988;White & Eaton, 1990). The results also indicate that field isolates of BTV-17 vary considerably in their patterns of neutralization by individual neutralizing MAbs (Letchworth & Appleton, 1983b;Greider & Schultz, 1990;MacLachlan et al, 1992).…”

Section: Discussionsupporting

confidence: 66%

“…Furthermore, recent studies with neutralizing monoclonal antibodies (MAbs) raised in mice against BTV-13 identified a neutralizing epitope also common to BTV-2 (Ristow et al, 1988). Neutralizing MAbs produced against Australian serotype BTV-1 bound but did not neutralize a variety of heterologous serotypes, suggesting that epitopes responsible for the definition of one BTV serotype may be preserved on other serotypes but not be involved in their neutralization (White & Eaton, 1990). …”

Section: Introductionmentioning

confidence: 99%

“…Epitopes responsible for the neutralization of BTV have been identified on only the major outer capsid protein VP2 (Huismans & Erasmus, 1981;Appleton & Letchworth, 1983;Letchworth & Appleton, 1983a;Mecham et al, 1986;Huismans et al, 1987;Roy et al, 1990) although the other outer capsid protein, VP5, might be indirectly involved in virus neutralization by its conformational influence on VP2 Mertens et al, 1989;Roy et al, 1990). Multiple neutralizing epitopes exist on BTV (Letchworth & Appleton, 1983 b;Gould & Eaton, 1990;Greider & Schultz, 1990;White & Eaton, 1990), and at least some of these epitopes are intimately associated on VP2 and contribute to a single, larger immunogenic domain (Heidner et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

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Neutralizing epitopes of the serotypes of bluetongue virus present in the United States

Rossitto

Maclachlan

1992

Journal of General Virology

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Neutralizing epitopes present on the five serotypes of bluetongue virus (BTV) which have been isolated in the United States were investigated with a panel of monoclonal antibodies (MAbs). Neutralizing MAbs were raised against the U.S. prototype viruses of BTV serotypes 2, 10, 1 l, 13 and 17, and were reacted with each virus in both neutralization and immune precipitation assays. All MAbs neutralized and precipitated VP2 of the virus against which they were raised. Five MAbs raised against BTV-l 0 also precipitated VP2 of the prototype strain of BTV-17, and four of these MAbs neutralized BTV-17. To characterize further the neutralizing epitopes of BTV, the MAbs raised against BTV-10 and BTV-17 were reacted by immune precipitation and neutralization assays with four field strains each of BTV-17 and BTV-10 isolated from ruminants in the U.S. All MAbs raised against BTV-10 both precipitated VP2 and neutralized the four field isolates of BTV-10, whereas none of the MAbs raised against BTV-17 reacted with these viruses. By contrast, all seven MAbs raised against BTV-17 and four of the seven MAbs raised against BTV-10 precipitated VP2 of the four BTV-17 field isolates. Another MAb raised against BTV-10 precipitated VP2 of three of the four field isolates of BTV-17. Whereas neutralization of the BTV-17 field isolates by several MAbs was inconsistent, all 10 isolates of BTV-10 and BTV-17 were neutralized by three MAbs raised against BTV-10. Results of this and other studies indicate that multiple neutralizing epitopes exist on each serotype of BTV. Some of these epitopes are conserved whereas others apparently vary in their significance to the neutralization of individual field isolates of BTV-17 and perhaps other BTV serotypes. These findings have implications for the future development of efficacious subunit vaccines to prevent BTV infection of ruminants.

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Section: Discussionsupporting

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Neutralizing epitopes of the serotypes of bluetongue virus present in the United States

Rossitto

Maclachlan

1992

Journal of General Virology

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“…The neutralizing antigenic determinants of orbiviruses reside on the VP2 outer capsid protein, but the other outer capsid protein (VP5) can influence the conformational nature of individual epitopes on VP2 (White and Eaton 1990, DeMaula et al 2000. The different serotypes of BTV segregate into clusters that sometimes demonstrate at least partial cross-neutralization by sera from naturally exposed animals.…”

Section: Immunity To Btv and Ehdv The Basis Of Vaccination Strategiesmentioning

confidence: 99%

Vaccines for Prevention of Bluetongue and Epizootic Hemorrhagic Disease in Livestock: A North American Perspective

Scott

James

2015

Vector-Borne and Zoonotic Diseases

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Bluetongue (BT) and epizootic hemorrhagic disease (EHD) are noncontagious, insect-transmitted diseases of domestic and wild ruminants caused by related but distinct viruses. There are significant gaps in our scientific knowledge and available countermeasures to control an outbreak of orbivirus-induced disease, whether BT or EHD. Both BT virus (BTV) and EHD virus (EHDV) cause hemorrhagic fevers in susceptible ruminants; however, BT is principally a disease of domestic livestock whereas EHD is principally a disease of certain species of wild, non-African ungulates, notably white-tailed deer. The live-attenuated (modified live virus [MLV]) vaccines available in the United States for use in small ruminant livestock do provide good protection against clinical disease following infection with the homologous virus serotype. Although there is increasing justification that the use of MLV vaccines should be avoided if possible, these are the only vaccines currently available in the United States. Specifically, MLVs are used in California to protect sheep against infection with BTV serotypes 10, 11, and 17, and a MLV to BTV serotype 10 is licensed for use in sheep throughout the United States. These MLV vaccines may need to continue to be used in the immediate future for protective immunization of sheep and goats against BT. There are currently no licensed vaccines available for EHD in the United States other than autogenous vaccines. If there is a need to rapidly develop a vaccine to meet an emerging crisis associated with either BTV or EHDV infections, development of an inactivated virus vaccine in a conventional adjuvanted formulation will likely be required. With two doses of vaccine (and in some instances just one dose), inactivated vaccines can provide substantial immunity to the epizootic serotype of either BTV or EHDV. This strategy is similar to that used in the 2006-2008 BTV serotype 8 outbreaks in northern Europe that provided vaccine to the field within 2 years of the initial incursion (by 2008). Further research and development are warranted to provide more efficacious and effective vaccines for control of BTV and EHDV infections.

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“…DeMaula et al (2000) showed that whereas most variants that were resistant to neutralization with individual neutralizing monoclonal antibodies (MAbs) had amino acid substitutions in key regions of VP2, the VP2 of one MAb-neutralization resistant variant virus was unchanged but this virus had a substitution in VP5, confirming unambiguously the importance of the conformational interaction between VP2 and VP5 in BTV neutralization. Individual neutralizing epitopes are sometimes conserved between serotypes in either a neutralizing or non-neutralizing conformation (Maclachlan et al, 1992;Pierce et al, 1995;Ristow et al, 1988;Rossitto and Maclachlan, 1992;White and Eaton, 1990). The presence of common neutralization epitopes between BTV serotypes is further confirmed by serological cross reactivity of certain serotypes of the virus, and by the fact that animals inoculated or immunized with one or more BTV serotypes can develop neutralizing antibodies against serotypes to which they were never exposed (Dungu et al, 2004;Rossitto and Maclachlan, 1992;Thomas, 1985).…”

Section: Antibody (Humoral) Immunitymentioning

confidence: 99%

The immune response of ruminant livestock to bluetongue virus: From type I interferon to antibody

Maclachlan

Henderson²,

Schwartz-Cornil³

et al. 2014

Virus Research

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Infection of ruminants with most (but not all) serotypes of bluetongue virus (BTV) leads to a highly blood cell-associated viremia that may be prolonged but not persistent. Furthermore, recovered animals are resistant to reinfection with the homologous virus serotype, which is the basis for vaccination strategies to prevent BTV infection and the clinical disease (bluetongue) that it causes in domestic livestock. BTV infection is initiated at the site of virus inoculation and the associated draining lymph node, from where the virus is then spread in lymph cells to the systemic circulation and secondary sites of replication. Replication of BTV in target cells, notably mononuclear phagocytic cells (dendritic cells and macrophages) and endothelium, leads to the generation of the innate and adaptive immune responses that mediate both initial virus clearance and subsequent resistance to infection with the homologous virus serotype. The goal of this review is to summarize current understanding of these innate and adaptive immune responses of animals to BTV infection.

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Conformation of the VP2 protein of bluetongue virus (BTV) determines the involvement in virus neutralization of highly conserved epitopes within the BTV serogroup

Cited by 43 publications

References 19 publications

Neutralizing epitopes of the serotypes of bluetongue virus present in the United States

Neutralizing epitopes of the serotypes of bluetongue virus present in the United States

Vaccines for Prevention of Bluetongue and Epizootic Hemorrhagic Disease in Livestock: A North American Perspective

The immune response of ruminant livestock to bluetongue virus: From type I interferon to antibody

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