Bluetongue virus 40051 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). Bluetongue disesase 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). 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). Baboon Papio cynocephalus 9556 Bank vole Clethrionomys glareolus 447135 Bear Ursus americanus 9643 Birds Passeroidea 175121 Brown Trout Salmo trutta 8032 Buffalo Bison bison 9901 Carnivores Vulpes 9625 Cat Felis catus 9685 Catfishes Siluriformes 7995 Cattle Bos taurus 9913 Chicken Gallus gallus 9031 Chimpanzee Pan troglodytes 9598 chinchillas Chinchillidae 10150 Copper Pheasant Syrmaticus soemmerringii 9067 Deer Cervus elaphus 9860 Deer mouse Peromyscus maniculatus 10042 Dog Canis familiaris 9615 Ducks Anas 8835 Ferret Mustela putorius furo 9669 Fish Hyperotreti 117565 Gerbil Gerbillina 10045 Goat Capra hircus 9925 Gray wolf Canis lupus 9612 Guinea pig Cavia porcellus 10141 Hamster Mesocricetus auratus 10036 Horse Equus caballus 9796 Human Homo sapiens 9606 Macaque Macaca fascicularis 9541 Mongolian Gerbil Meriones unguiculatus 10047 Monkey Platyrrhini 9479 Mouse Mus musculus 10090 None None Parrot Psittacidae 9224 Pig Sus scrofa 9823 Rabbit Oryctolagus cuniculus 9986 Rainbow trout Oncorhynchus mykiss 8022 Rat Rattus 10114 Raven Corvus corax 56781 sei whale Balaenoptera borealis 9768 Sheep Ovis aries 9940 Squirrel Spermophilus richardsonii 37591 Tree shrew Tupaiidae 9393 Trouts, salmons & chars Salmoninae 504568 Turkey Meleagris gallopavo 9103 Vole Microtus ochrogaster 79684 Water buffalo Bubalus bubalis 391902 ALVAC-BTV-CP(VP2/VP5) VO_0004732 Recombinant vector vaccine Research Intramuscular injection (i.m.) (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 Intramuscular injection (i.m.) ALVAC-BTV-VP2/VP5 VO_0004726 Recombinant vector vaccine Research Intramuscular injection (i.m.) 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). Intramuscular injection (i.m.) VO_0000287 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). The field strain of BTV-17 was used for challenging (Boone et al., 2007). Bluetongue Modified Live Virus Vaccine (USDA: 1061.00) Colorado Serum Company VO_0001816 Live vaccine Licensed USA BoHV-4-A-IgK-VP2gD VO_0004686 Recombinant vector vaccine Research Other 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). Other Mice eveloped serum neutralizing antibodies against BTV . α/β interferon receptor knockout (IFNAR(-/-)) mice IFNAR(-/-) mice intraperitoneally inoculated twice with BoHV-4-A-IgK-VP2gDtm at different time points. VO_0000287 Vaccinated mice showed a strongly reduced viremia and a longer survival time after challenge (Franceschi et al., 2011). 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). a lethal dose of BTV-8 as used for challenge (Franceschi et al., 2011). rCPV-BTV-Cpox VO_0004788 Recombinant vector vaccine Research Intramuscular injection (i.m.) 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). Intramuscular injection (i.m.) Sheep were immunized with BTV recombinant capripoxviruses (BTV-Cpox) (Perrin et al., 2007). VO_0000287 Sheep challenged 3 weeks after BTV-Cpox vaccination exhibited partial protection (Perrin et al., 2007). The sheep were challenged with a virulent strain of BTV-2 (Perrin et al., 2007). SG33-VP2/5 VO_0004706 Recombinant vector vaccine Research Other MYXV expressing the immunodominant VP2 protein (SG33-VP2) (Top et al., 2012) Other The SG33-VP2 vector promoted the production of neutralising antibodies (Maclachlan et al., 2009). Sheep were injected twice with an MYXV expressing the immunodominant VP2 protein (SG33-VP2) (Top et al., 2012). VO_0000287 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). Boone et al., 2007 journal Boone JD, Balasuriya UB, Karaca K, Audonnet JC, Yao J, He L, Nordgren R, Monaco F, Savini G, Gardner IA, Maclachlan NJ 2007 25 4 672-678 Vaccine Bouet-Cararo et al., 2014 journal 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 2014 9 11 e111605 PloS one Franceschi et al., 2011 journal Franceschi V, Capocefalo A, Calvo-Pinilla E, Redaelli M, Mucignat-Caretta C, Mertens P, Ortego J, Donofrio G 2011 29 16 3074-3082 Vaccine Legisa et al., 2015 journal Legisa DM, Perez Aguirreburualde MS, Gonzalez FN, Marin-Lopez A, Ruiz V, Wigdorovitz A, Martinez-Escribano JA, Ortego J, Dus Santos MJ 2015 33 22 2614-2619 Vaccine Maclachlan et al., 2009 journal Maclachlan NJ, Drew CP, Darpel KE, Worwa G 2009 141 1 1-16 Journal of comparative pathology Perrin et al., 2007 journal Perrin A, Albina E, Bréard E, Sailleau C, Promé S, Grillet C, Kwiatek O, Russo P, Thiéry R, Zientara S, Cêtre-Sossah C 2007 25 37-38 6774-6783 Vaccine Top et al., 2012 journal Top S, Foucras G, Deplanche M, Rives G, Calvalido J, Comtet L, Bertagnoli S, Meyer G 2012 30 9 1609-1616 Vaccine Wang et al., 2013 journal Wang WS, Sun EC, Liu NH, Yang T, Xu QY, Qin YL, Zhao J, Feng YF, Li JP, Wei P, Zhang CY, Wu DL 2013 162 2-4 631-642 Veterinary microbiology Wiki: Bluetongue website http://en.wikipedia.org/wiki/Bluetongue