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Bluetongue virus

Table of Contents
  1. General Information
    1. NCBI Taxonomy ID
    2. Disease
    3. Introduction
    4. Microbial Pathogenesis
    5. Host Ranges and Animal Models
  2. Vaccine Related Pathogen Genes
    1. VP2 (Protective antigen)
    2. VP5 (Protective antigen)
    3. VP7 (Protective antigen)
  3. Vaccine Information
    1. ALVAC-BTV-CP(VP2/VP5)
    2. ALVAC-BTV-VP2/VP5
    3. Bluetongue Modified Live Virus Vaccine (USDA: 1061.00)
    4. BoHV-4-A-IgK-VP2gD
    5. rCPV-BTV-Cpox
    6. SG33-VP2/5
  4. References
I. General Information
1. NCBI Taxonomy ID:
40051
2. Disease:
Bluetongue disesase
3. Introduction
Bluetongue disease or catarrhal fever is a non-contagious, non-zoonotic, insect-borne, viral disease of ruminants, mainly sheep and less frequently cattle, goats, buffalo, deer, dromedaries and antelope. It is caused by the Bluetongue virus. There are no reports of human transmission. Although the tongues of human patients with some types of heart disease may be blue, this sign is not related to bluetongue disease. Bluetongue is caused by the pathogenic virus, Bluetongue virus (BTV), of the genus Orbivirus, is a member of the Reoviridae family. There are 24 serotypes. It is transmitted by a midge, Culicoides imicola and other culicoids. Major signs are high fever, excessive salivation, swelling of the face and tongue and cyanosis of the tongue. Swelling of the lips and tongue gives the tongue its typical blue appearance, though this sign is confined to a minority of the animals. Nasal symptoms may be prominent, with nasal discharge and stertorous respiration. Some animals also develop foot lesions, beginning with coronitis, with consequent lameness. In sheep, this can lead to knee-walking. In cattle, constant changing of position of the feet gives bluetongue the nickname "The Dancing Disease". Torsion of the neck (opisthotonos or torticollis) is observed in severely affected animals. Not all animals develop symptoms, but all those that do lose condition rapidly, and the sickest die within a week. For affected animals which do not die, recovery is very slow, lasting several months (Wiki: Bluetongue).
4. Microbial Pathogenesis
The pathogenesis of BTV infection is similar in sheep and cattle and, most probably, all species of ruminants. However, there are marked differences in the severity of disease that occurs in different ruminant species or breeds after BTV infection, and infection of the same species or sheep breed with different virus strains. After cutaneous instillation of BTV (by inoculation or through the bite of a BTV-infected Culicoides vector) the virus travels to the regional lymph node, where initial replication occurs. The virus then is disseminated to a variety of tissues throughout the body, where replication occurs principally in mononuclear phagocytic and endothelial cells, lymphocytes and perhaps other cell types. Viraemia is highly cell associated and may be prolonged but not persistent in domestic ruminants. BTV promiscuously associates with all blood cells during viraemia, thus titres of virus in each cell fraction are proportionate to the numbers of each cell type; specifically, BTV is quantitatively associated most with platelets and erythrocytes and, because of the short lifespan of platelets, virus is largely or exclusively associated with erythrocytes late in the course of BTV infection of ruminants. BTV infection of erythrocytes facilitates both prolonged infection of ruminants and infection of haematophagous insect vectors that feed on viraemic ruminants, and infectious virus can co-circulate for several weeks with high titres of neutralizing antibody (Maclachlan et al., 2009).
5. Host Ranges and Animal Models
Bluetongue infects ruminants, mainly sheep but also cattle, goats, buffalo, deer, dromedaries, and antelope. It is transmitted by a midge, Culicoides imicola and other culicoids (Wiki: Bluetongue).
1. VP2
  • Gene Name : VP2
  • Sequence Strain (Species/Organism) : Bluetongue virus
  • NCBI Protein GI : AGS78451
  • Other Database IDs : CDD:279269
  • Taxonomy ID : 40051
  • Protein Name : VP2
  • Protein pI : 6.92
  • Protein Weight : 77652.84
  • Protein Length : 750
  • Protein Note : Orbivirus outer capsid protein VP2; pfam00898
  • Protein Sequence : Show Sequence
    >AGS78451.1 VP2, partial [Bluetongue virus]
    MDGLGIPIYKQGFPEHLLHGYEFTIDSSTKIQSVGGRHDVTKLPEMNAYDIKAESIRTALWYNPVRNDGF
    VLPRVLDITLRGYDGKRAVIDSSKHKIFHTDERWVQWMMKDSMDAQPLKVGLDDRTQKIAHSLHNCVVKI
    DSKKADTTSYHIEPIEDPSKGCLHTRAMLWNHLVRIEMSHAAQEIAYTLKPTYDIVVHAERRDRSQPFQP
    GDQTLINFGRGQKVQMNHNSYEKMVEGLAHLVIRGKTPELIRDEIAKLDEICNRWIRSRHDPGEIKAYEL
    CKILSTVGRKMLDQEKEPADEASLSIRFQEAIDNKFRQHDPERLKIFEHRNQRRDEDRFYILLMIAASDT
    FNTRIWWSNPYPCLRGTLMASETKLGDVYSMIRSWYDWSVRPTYTPYEKSREQEKYIYGRVNLFDYVAEP
    GTKIIHWEYKLNQQTKDITYEQGNPCDLFPDDDEAIVTKFDDVAYGQMVSDLINGGWDQERFKMHKILKS
    QGNVLTIDFEKDAKLTSNEGVTMPEYFDKWIIAPMFNAKLRIKHSEIAQRRNDDPMVKRTLSPIAFDPIV
    LQRLTLARYYDIRPAIMGQALSRQQGQSTYDEEVSKIEGYAEILQRRGIVQIPKKPCPTVTAQYTLERYA
    LFLINILEQHVIQSTDEDVIYSHPRVDYKLEIYGESIVDISQIVIFVFDFLFERRRTVRGVYESR
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : (Legisa et al., 2015)
2. VP5
  • Gene Name : VP5
  • Sequence Strain (Species/Organism) : Bluetongue virus
  • NCBI Protein GI : AEP83825
  • Other Database IDs : CDD:279272
  • Taxonomy ID : 40051
  • Protein Name : VP5
  • Protein pI : 6.31
  • Protein Weight : 56857.19
  • Protein Length : 570
  • Protein Note : Orbivirus outer capsid protein VP5; pfam00901
  • Protein Sequence : Show Sequence
    >AEP83825.1 VP5 [Bluetongue virus]
    MGKIIKSLSRFGKKVGNALTSNTAKKIYSTIGKAAERFAESEIGSAAIDGLVQGSVHSIMTGESYGESVK
    QAVLLNVLGAGDEIPDPLSPGERGIQMKIKEIEEEQRNELVRLKHGKEITKKFGEELEEIYQFMNGEVKD
    EEEQEEQYKVLCKAVNSYEKLLIAENDKMHILARALQREAAERTEAESTMVKEYRQKIDALKAAIEIERD
    GMQEEAIQEIAGMTADVLEAASEEVPLVGSGMASAIATGRAIEGAYKLKKVINALSGIDLSHLRTPKIEP
    TMVATTLEHRFEDIPDKKLAMSILAKNNAITANTREIQHIKEEILPKFKKVMDEEKELEGIDDKKIHPRV
    MMRFKVPRSQQPQIHIYSAPWDSDDVFFFHCISHFHANESFFLGFDLGIDVVHFEDLAAHWHALGAAQEA
    KGRTLNEAYREFLNLAIGSTYTSPMHARRMIRSKTVHPIYLGSMHYDITYDTLKSNAQRIVYDDELQMHI
    LRGPLHFQRRAILGALKFGVKVLGDKIDVPLFLKNA
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : (Wang et al., 2013)
3. VP7
  • Gene Name : VP7
  • Sequence Strain (Species/Organism) : Bluetongue virus
  • NCBI Protein GI : AEP83826
  • Other Database IDs : CDD:279268
  • Taxonomy ID : 40051
  • Protein Name : VP7
  • Protein pI : 6.68
  • Protein Weight : 36377.11
  • Protein Length : 390
  • Protein Note : Orbivirus inner capsid protein VP7; pfam00897
  • Protein Sequence : Show Sequence
    >AEP83826.1 VP7 [Bluetongue virus]
    MDTIAARALTVMRACATLQEARIVLEANVMEILGIAINRYNGLTLRGVTMRPTSLAQRNEMFFMCLDMML
    SAAGINVGPISPDYTQHMATIGVLATPEIPFTTEAANEIARVTGETSTWGPARQPYGFFLETEEVYQPGR
    WFMRAAQVVTPVVCGPDMIQVSLNAGARGDVQQIFQGRNDPMMIYLVWRRIENFSMPQGNSQRTLAGVTV
    SVGGVDMRAGRIIAWDGQAVLQIHNPTQQNAMVQIQVVFYISMDKTLNQYPALTAEIFNVYSFRDHTWHG
    LRTAILNRTTLPNMLPPIFPPNDRDSILTILLLSTLADVYSVLRPEFAIHGVNPMPGPLTRAIARAAYA
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : (Bouet-Cararo et al., 2014)
III. Vaccine Information
1. ALVAC-BTV-CP(VP2/VP5)
a. Vaccine Ontology ID:
VO_0004732
b. Type:
Recombinant vector vaccine
c. Status:
Research
d. Host Species for Licensed Use:
Baboon
e. Preparation
(Boone et al., 2007) recombinant canarypox virus vector (BTV-CP) co-expressing synthetic genes encoding the two outer capsid proteins (VP2 and VP5) of BTV serotype 17
f. Immunization Route
Intramuscular injection (i.m.)
2. ALVAC-BTV-VP2/VP5
a. Vaccine Ontology ID:
VO_0004726
b. Type:
Recombinant vector vaccine
c. Status:
Research
d. Host Species for Licensed Use:
Baboon
e. Preparation
A recombinant canarypox virus vector was used to co-express genes encoding the VP2 and VP5 outer capsid proteins of bluetongue virus (Boone et al., 2007).
f. Immunization Route
Intramuscular injection (i.m.)
g. Sheep Response
  • Vaccine Immune Response Type: VO_0000287
  • Challenge Protocol: The field strain of BTV-17 was used for challenging (Boone et al., 2007).
  • Efficacy: The sheep vaccinated with the recombinant canarypox virus vectored vaccine were resistant to challenge with a field strain of BTV-17 (Boone et al., 2007).
3. Bluetongue Modified Live Virus Vaccine (USDA: 1061.00)
a. Manufacturer:
Colorado Serum Company
b. Vaccine Ontology ID:
VO_0001816
c. Type:
Live vaccine
d. Status:
Licensed
e. Location Licensed:
USA
f. Host Species for Licensed Use:
Sheep
4. BoHV-4-A-IgK-VP2gD
a. Vaccine Ontology ID:
VO_0004686
b. Type:
Recombinant vector vaccine
c. Status:
Research
d. Host Species for Licensed Use:
Cattle
e. Preparation
BoHV-4-based vector cloned as a bacterial artificial chromosome (BAC) was engineered to express the bluetongue virus (BTV) immune-dominant glycoprotein VP2 provided of a heterologous signal peptide to its amino terminal and a trans-membrane domain to its carboxyl terminal (IgK-VP2gDtm), to allow VP2 expression targeting to the cell membrane fraction (Franceschi et al., 2011).
f. Immunization Route
Other
g. Mouse Response
  • Host Strain: α/β interferon receptor knockout (IFNAR(-/-)) mice
  • Vaccination Protocol: IFNAR(-/-) mice intraperitoneally inoculated twice with BoHV-4-A-IgK-VP2gDtm at different time points.
  • Vaccine Immune Response Type: VO_0000287
  • Immune Response: Mice eveloped serum neutralizing antibodies against BTV .
  • Side Effects: A pre-challenge experiment was performed to test BoHV-4 safety on adult α/β interferon receptor knockout (IFNAR(-/-)) mice, a newly generated bluetongue laboratory animal model. BoHV-4 infected IFNAR(-/-) mice did not show clinical signs even following the inoculation of BoHV-4 intra-cerebrally, although many areas of the brain got transduced (Franceschi et al., 2011).
  • Challenge Protocol: a lethal dose of BTV-8 as used for challenge (Franceschi et al., 2011).
  • Efficacy: Vaccinated mice showed a strongly reduced viremia and a longer survival time after challenge (Franceschi et al., 2011).
5. rCPV-BTV-Cpox
a. Vaccine Ontology ID:
VO_0004788
b. Type:
Recombinant vector vaccine
c. Status:
Research
d. Host Species for Licensed Use:
Baboon
e. Preparation
BTV recombinant capripoxviruses (BTV-Cpox) individually expressing four different genes encoding two capsid proteins (VP2 and VP7) and two non-structural proteins (NS1, NS3) of BTV serotype 2 (BTV-2) (Perrin et al., 2007).
f. Immunization Route
Intramuscular injection (i.m.)
g. Sheep Response
  • Vaccination Protocol: Sheep were immunized with BTV recombinant capripoxviruses (BTV-Cpox) (Perrin et al., 2007).
  • Vaccine Immune Response Type: VO_0000287
  • Challenge Protocol: The sheep were challenged with a virulent strain of BTV-2 (Perrin et al., 2007).
  • Efficacy: Sheep challenged 3 weeks after BTV-Cpox vaccination exhibited partial protection (Perrin et al., 2007).
6. SG33-VP2/5
a. Vaccine Ontology ID:
VO_0004706
b. Type:
Recombinant vector vaccine
c. Status:
Research
d. Host Species for Licensed Use:
Sheep
e. Preparation
MYXV expressing the immunodominant VP2 protein (SG33-VP2) (Top et al., 2012)
f. Immunization Route
Other
g. Sheep Response
  • Vaccination Protocol: Sheep were injected twice with an MYXV expressing the immunodominant VP2 protein (SG33-VP2) (Top et al., 2012).
  • Vaccine Immune Response Type: VO_0000287
  • Immune Response: The SG33-VP2 vector promoted the production of neutralising antibodies (Maclachlan et al., 2009).
  • Efficacy: The SG33-VP2 vector expressing VP2 partially protected sheep against disease after challenge with a highly virulent strain of serotype-8 bluetongue virus (BTV-8) (Top et al., 2012).
IV. References
1. Boone et al., 2007: Boone JD, Balasuriya UB, Karaca K, Audonnet JC, Yao J, He L, Nordgren R, Monaco F, Savini G, Gardner IA, Maclachlan NJ. Recombinant canarypox virus vaccine co-expressing genes encoding the VP2 and VP5 outer capsid proteins of bluetongue virus induces high level protection in sheep. Vaccine. 2007; 25(4); 672-678. [PubMed: 17059856].
2. Bouet-Cararo et al., 2014: Bouet-Cararo C, Contreras V, Caruso A, Top S, Szelechowski M, Bergeron C, Viarouge C, Desprat A, Relmy A, Guibert JM, Dubois E, Thiery R, Bréard E, Bertagnoli S, Richardson J, Foucras G, Meyer G, Schwartz-Cornil I, Zientara S, Klonjkowski B. Expression of VP7, a Bluetongue virus group specific antigen by viral vectors: analysis of the induced immune responses and evaluation of protective potential in sheep. PloS one. 2014; 9(11); e111605. [PubMed: 25364822].
3. Franceschi et al., 2011: Franceschi V, Capocefalo A, Calvo-Pinilla E, Redaelli M, Mucignat-Caretta C, Mertens P, Ortego J, Donofrio G. Immunization of knock-out α/β interferon receptor mice against lethal bluetongue infection with a BoHV-4-based vector expressing BTV-8 VP2 antigen. Vaccine. 2011; 29(16); 3074-3082. [PubMed: 21320537].
4. Legisa et al., 2015: Legisa DM, Perez Aguirreburualde MS, Gonzalez FN, Marin-Lopez A, Ruiz V, Wigdorovitz A, Martinez-Escribano JA, Ortego J, Dus Santos MJ. An experimental subunit vaccine based on Bluetongue virus 4 VP2 protein fused to an antigen-presenting cells single chain antibody elicits cellular and humoral immune responses in cattle, guinea pigs and IFNAR(-/-) mice. Vaccine. 2015; 33(22); 2614-2619. [PubMed: 25858859].
5. Maclachlan et al., 2009: Maclachlan NJ, Drew CP, Darpel KE, Worwa G. The pathology and pathogenesis of bluetongue. Journal of comparative pathology. 2009; 141(1); 1-16. [PubMed: 19476953].
6. Perrin et al., 2007: Perrin A, Albina E, Bréard E, Sailleau C, Promé S, Grillet C, Kwiatek O, Russo P, Thiéry R, Zientara S, Cêtre-Sossah C. Recombinant capripoxviruses expressing proteins of bluetongue virus: evaluation of immune responses and protection in small ruminants. Vaccine. 2007; 25(37-38); 6774-6783. [PubMed: 17669563].
7. Top et al., 2012: Top S, Foucras G, Deplanche M, Rives G, Calvalido J, Comtet L, Bertagnoli S, Meyer G. Myxomavirus as a vector for the immunisation of sheep: protection study against challenge with bluetongue virus. Vaccine. 2012; 30(9); 1609-1616. [PubMed: 22244980].
8. Wang et al., 2013: Wang WS, Sun EC, Liu NH, Yang T, Xu QY, Qin YL, Zhao J, Feng YF, Li JP, Wei P, Zhang CY, Wu DL. Identification of three novel linear B-cell epitopes on the VP5 protein of BTV16. Veterinary microbiology. 2013; 162(2-4); 631-642. [PubMed: 23290575].
9. Wiki: Bluetongue: Wiki: Bluetongue [http://en.wikipedia.org/wiki/Bluetongue]