Orbiviruses and Bluetongue Virus

Peter Mertens, Institute for Animal Health, Newbury, Berkshire, UK
Houssam Attoui, Institute for Animal Health, Newbury, Berkshire, UK

Published online: December 2009

DOI: 10.1002/9780470015902.a0001010.pub2

Bluetongue virus (BTV) is the type species of the genus Orbivirus within the family Reoviridae (the largest double-stranded ribonucleic acid (dsRNA) virus family). BTV is an arthropod-borne pathogen that is transmitted by the bites of its vector, the Culicoides midges, which transmit the virus between its ruminant hosts. The virus can infect most species of domestic and wild ruminants. BT clinical signs are most common in sheep and some species of deer. In recent years, the distribution of BTV has changed considerably, particularly in Europe. New outbreaks have occurred each year from 1998 to 2006 in southern and central Europe, involving several strains from five different serotypes. In 2006, BTV serotype 8 caused an outbreak approximately 5° further north in Europe than ever before, infecting ruminants in a wide area across northern Europe and bringing the number of European serotypes to six. A new virus (Toggenburg virus) has been identified in goats from Switzerland in 2008 and designated as the twenty-fifth serotype of BTV.

Key concepts:

  • Genus Orbivirus is the most diverse genus of family Reoviridae containing 22 virus species.
  • Bluetongue disease affects mainly sheep causing severe clinical signs and high mortality.
  • Bluetongue virus is transmitted by competent species of Culicoides midges.
  • Phylogenetic analysis identifies two major groups of orbiviruses, those with their subcore shell protein (T2 protein) being the VP2 and those with the T2 being VP3. Orbiviruses are nonturreted members of family Reoviridae, and the atomic structure of BTV core has been determined.

Keywords: Orbivirus; Reoviridae; dsRNA virus; BTV; bluetongue; Culicoides

Figure 1. Phylogenetic trees for (a) the ‘variable’ orbivirus outer capsid protein VP2, and (b) the ‘conserved’ orbivirus subcore shell protein (T2). (a) VP2 is the most variable outer capsid protein and is the major serotype specific and neutralization antigen. (b) The T2 protein is the VP3 for the Culicoides-borne orbiviruses and the VP2 in mosquito-borne and tick-borne orbiviruses (the phylogenetic tree is based on the sequences encompassing amino acids 393 to 548 relative to BTV-10 sequence). BTV, Bluetongue virus; AHSV, African horsesickness virus, CHUV, Chuzan virus; PHSV, Peruvian horsesickness virus; ELSV, Elsey virus; YUOV, Yunnan orbivirus (P, Peru; Aus, Australia; Ch, China); BRDV, Broadhaven virus; DAGV, Daguillar virus; PRV, Paroo River virus; PIAV, Picola virus.
Figure 2. Unrooted neighbour-joining (NJ) tree showing the relationships between deduced amino acid sequences of VP2/Seg-2 from the 24 BTV serotypes. This NJ tree was constructed using MEGA program version 3.1 using the p-distance algorithm and the full-length VP2 sequences of the 24 BTV types. The different serotypes (indicated by dotted circles) are distinct but show some relationships (green bubbles) that mirror the serological relatedness (cross-reactions) that are known to exist between different serotypes. These groupings are reflected in the nucleotide sequences of genome segment 2 and the 10 distinct groups have previously been identified as nucleotypes A–J.
Figure 3. Diagram of the replication cycle of Bluetongue virus (BTV). BTV particles bind to cell surface receptors and are transported, via clathrin-coated pits, to endosomes. The outer capsid layer of BTV is pH sensitive and may be modified, or lost, as the contents of the endosome become more acidic. An unknown mechanism, possibly triggered by the low pH, allows the virus core to leave the early endosome, crossing the endosomal membrane and entering the cytoplasm. Once in the cytoplasm the core synthesizes mRNA copies (shown in blue) of the viral genome segments. These act as templates for the synthesis of viral proteins (shown in green) by the host cell ribosomes. The mRNAs also associate with newly synthesized viral proteins to form nascent progeny core particles. The assembly process and negative-strand RNA synthesis within the nascent particles, to reform the dsRNA genome segments, take place within the viral inclusion bodies (shown in red). These are seen by electron microscopy as granular matrices that are initially associated with the infecting parental core. As the progeny virus cores leave the viral inclusion body, outer capsid proteins are added to form mature virus particles, which can leave the cell by budding, extrusion or cell lysis. Released particles can reinfect the same or other cells, helping to spread the infection and increasing the chances of genome segment reassortment. The nucleus is not shown in this diagram and is not believed to play any significant role in the processes of BTV replication.
Figure 4. Electron micrographs of (a) Bluetongue virus 1 (South Africa) virus particles; (b) infectious subviral particles; and (c) core particles. Particles were purified and stained with 2% methylamine tungstate.
Figure 5. Bluetongue virus (BTV) structure. (a) Model of the outer capsid layer of BTV particles, from cryoelectron microscopy. Courtesy of Hewat et al., 1992 with permission. Structures thought to represent VP2 shown in blue and VP5 shown in yellow. Models from X-ray crystallography of the native core particle. The outer core surface (b), composed of 260 trimers of VP7(T13), arranged with T=13 symmetry. The chemically identical but structurally different trimers are coloured and named in order of increasing distance from the 5-fold axes of symmetry (P, red; Q, orange; R, yellow; S, green and T, blue; situated at the 3-fold axes). (c) The BTV-1 subcore shell is composed of 120 copies of VP3(T2), arranged with T=2 symmetry. The chemically identical but structurally different ‘A’ (green) and ‘B’ (red) molecules are shown. (d) The dsRNA genome can be modelled as concentric shells of RNA, with helices in the outermost shell spiraling around and away from the position of TCs, that are situated in holes in the RNA layers, at the 5-fold axes of the icosahedral particle. Courtesy of DI Stuart, J Grimes, P Gouet, J Diprose, R Malby and PPC Mertens.
Figure 6. Cross-sectional diagram of the Bluetongue virus particle.
Figure 7. The atomic structure of the BTV capping enzyme VP4(CaP) coloured by domain. From the N- to the C-terminus: the kinase-like (KL, in blue) domain, which is thought to interact with the polymerase; the N7-methyltransferase (N7MT, in green); the O2-methyltransferase (O2MT, in red) and the guanylyltransferase (GTase, in yellow).
Figure 8. The atomic structure of the BTV NS2 N-terminal domain. The structure is composed predominantly of two sheets arranged as a sandwich (dimer). The putative RNA-binding domain is towards the bottom of the molecule (circled with dashed red line).
Figure 9. A sheep infected by Bluetongue virus serotype 4. Excess salivation and associated respiratory distress observed in a sheep at six days postinfection with BTV.
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 References
    Brookes SM, Hyatt AD and Eaton BT (1993) Characterization of virus inclusion bodies in bluetongue virus-infected cells. Journal of General Virology 74: 525–530.
    DeMaula CD, Bonneau KR and MacLachla NJ (2000) Changes in the outer capsid proteins of bluetongue virus serotype ten that abrogate neutralization by monoclonal antibodies. Virus Research 67: 59–66.
    Devi R, Burroughs JN, Mertens PPC et al. (1998) Capping and methylation of mRNA by purified recombinant VP4 protein of bluetongue virus. Proceedings of the National Academy of Sciences of the USA 95: 13537–13542.
    book Gorman BM, Ghaleb HW, Huismans H et al. (1985) "WHO/FAO working team report: molecular virology". In: Barger T and Jochim MM (eds) Bluetongue and Related Orbiviruses, pp. 689–695. New York: Liss.
    Gouet P, Diprose JM, Grimes JM et al. (1999) The highly ordered double stranded RNA genome of bluetongue virus revealed by crystallography. Cell 97: 481–490.
    Gould AR and Hyatt AD (1994) The orbivirus genus: diversity, structure, replication and phylogenetic relationships. Comparative Immunology, Microbiology and Infectious Diseases 17: 163–188.
    Grimes JM, Burroughs JN, Gouet P et al. (1998) The atomic structure of the bluetongue virus core. Nature 395: 470–478.
    Hassan SS and Roy P (1999) Expression and functional characterization of bluetongue virus VP2 protein: role in cell entry. Journal of Virology 73: 9832–9842.
    Hassan SH, Wirblich C, Forzan M and Roy P (2001) Expression and functional characterization of bluetongue virus VP5 protein: role in cellular permeabilization. Journal of Virology 75: 8356–8367.
    Hewat EA, Booth TF and Roy P (1992) Structure of bluetongue virus particles by cryoelectron microscopy. Journal of Structural Biology 109: 61–69.
    Hyatt AD, Zhao Y and Roy P (1993) Release of bluetongue virus-like particles from insect cells is mediated by BTV non-structural protein NS3/3a. Virology 193: 592–603.
    Loudon PT and Roy P (1991) Assembly of five bluetongue virus proteins expressed by recombinant baculoviruses: inclusion of the largest protein VP1 in the core and virus like particles. Virology 180: 798–802.
    Maan S, Maan NS, Ross-smith NS et al. (2008) Sequence analysis of bluetongue virus serotype 8 from the Netherlands 2006 and comparison to other European strains. Virology 377: 308–318.
    Maan S, Maan NS, Samuel AR et al. (2007) Analysis and phylogenetic comparisons of full-length VP2 genes of the 24 bluetongue virus serotypes. Journal of General Virology 88: 621–630.
    Mertens PP, Burroughs JN and Anderson J (1987) Purification and properties of virus particles, infectious subviral particles, and cores of bluetongue virus serotypes 1 and 4. Virology 157: 375–386.
    book Mertens PPC, Attoui H, Duncan R and Dermody TS (2005) "Reoviridae". In: Fauquet CM, Mayo MA, Maniloff J, Desselberger U and Ball LA (eds) Virus Taxonomy. Eighth Report of the International Committee on Taxonomy of Viruses, pp. 447–454. London: Elsevier/Academic Press.
    Mertens PPC, Brown F and Sangar DV (1984) Assignment of the genome segments of bluetongue virus type 1 to the proteins which they encode. Virology 135: 207–217.
    Mertens PPC, Burroughs JN, Walton A et al. (1996) Enhanced infectivity of modified bluetongue virus particles for two insect cell lines and for two Culicoides vector species. Virology 217: 582–593.
    Nason EL, Rothagel R, Mukherjee SK et al. (2004) Interactions between the inner and outer capsids of bluetongue virus. Journal of Virology 78: 8059–8067.
    Pedley S, Mohamed EH and Mertens PPC (1988) Analysis of the genome segments of six different bluetongue virus isolates using RNA–RNA hybridization: a generalised coding assignment for bluetongue virus. Virus Research 10: 381–390.
    Stauber N, Martinez-Costas J, Sutton G et al. (1997) Bluetongue virus VP6 protein binds ATP and exhibits an RNA-dependent ATPase function and a helicase activity that catalyze the unwinding of double-stranded RNA substrates. Journal of Virology 71: 7220–7226.
    Schoehn G, Moss SR, Nuttall PA and Hewat EA (1997) Structure of Broadhaven virus by cryoelectron microscopy: correlation of structural and antigenic properties of Broadhaven virus and bluetongue virus outer capsid proteins. Virology 235: 191–200.
    Stuart D, Gouet P, Grimes J et al. (1998) Structural studies of Orbivirus particles. Archives of Virology Supplement 14: 235–250.
    Stuart DI, Grimes JM (2006) Structural studies on orbivirus proteins and particles. Current Topics in Microbiology and Immunology 309: 221–244.
    Urakawa T, Ritter DG and Roy P (1989) Expression of the largest RNA segment and synthesis of VP1 protein of bluetongue virus in insect cells by recombinant baculovirus: association of VP1 protein with RNA polymerase activity. Nucleic Acids Research 17: 7395–7401.
    Wade-Evans AM, Romero CH, Mellor P et al. (1996) Expression of the major core structural protein (VP7) of bluetongue virus, by a recombinant capripox virus, provides partial protection of sheep against a virulent heterotypic bluetongue virus challenge. Virology 220: 227–231.
 Further Reading
    Hill CL, Booth TF, Prasad BVV et al. (1999) The structure of a cypovirus and the functional organisation of dsRNA viruses. Nature Structural Biology 6: 565–568.
    other Mellor PS, Baylis M, Hamblin C, Calisher CH and Mertens PPC (eds) (1998) African horse sickness. Archives of Virology Supplement 14: 1–342.
    book Mertens PPC (1999) "Orbiviruses and coltiviruses: general features". In: Webster RG and Granoff A (eds) Encyclopedia of Virology, 2nd edn, pp. 1043–1061. London: Academic Press.
    Roy P (1989) Bluetongue virus genetics and genome structure. Virus Research 13: 179–206.
    Roy P (1989) Bluetongue virus proteins. Journal of General Virology 73: 3051–3064.
    other Roy P and Gorman BM (eds) (1990) Bluetongue viruses. Current Topics in Microbiology and Immunology 162: 1–200.
    book Roy P and Mertens PPC (1999) "Orbiviruses and coltiviruses: molecular biology". In: Webster RG and Granoff A (eds) Encyclopedia of Virology, 2nd edn, pp. 1062–1074. London: Academic Press.

Related Sub-Topics:

Virus Diseases | RNA Viruses | Viruses Infecting Animals
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Article Title: Orbiviruses and Bluetongue Virus
 
How to Cite close
Mertens, Peter, and Attoui, Houssam(Dec 2009) Orbiviruses and Bluetongue Virus. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001010.pub2]