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Published in: Virology Journal 1/2010

Open Access 01-12-2010 | Research

Molecular characterisation of virulence graded field isolates of myxoma virus

Authors: Kevin P Dalton, Ines Nicieza, Aroa Baragaño, Jose Manuel Martín Alonso, Francisco Parra

Published in: Virology Journal | Issue 1/2010

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Abstract

Background

Myxoma virus (MV) has been endemic in Europe since shortly after its deliberate release in France in 1952. While the emergence of more resistant hosts and more transmissible and attenuated virus is well documented, there have been relatively few studies focused on the sequence changes incurred by the virus as it has adapted to its new host. In order to identify regions of variability within the MV genome to be used for phylogenetic studies and to try to investigate causes of MV strain attenuation we have molecularly characterised nine strains of MV isolated in Spain between the years 1992 and 1995 from wide ranging geographic locations and which had been previously graded for virulence by experimental infection of rabbits.

Results

The findings reported here show the analysis of 16 genomic regions accounting for approximately 10% of the viral genomes. Of the 20 genes analysed 5 (M034L, M069L, M071L, M130R and M135R) were identical in all strains and 1 (M122R) contained only a single point mutation in an individual strain. Four genes (M002L/R, M009L, M036L and M017L) showed insertions or deletions that led to disruption of the ORFs.

Conclusions

The findings presented here provide valuable tools for strain differentiation and phylogenetic studies of MV isolates and some clues as to the reasons for virus attenuation in the field.
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Literature
1.
go back to reference Muller A, Silva E, Abrantes J, Esteves PJ, Ferreira PG, Carvalheira JC, Nowotny N, Thompson G: Partial sequencing of recent Portuguese myxoma virus field isolates exhibits a high degree of genetic stability. Vet Microbiol 2010, 140: 161-166. 10.1016/j.vetmic.2009.07.028PubMedCrossRef Muller A, Silva E, Abrantes J, Esteves PJ, Ferreira PG, Carvalheira JC, Nowotny N, Thompson G: Partial sequencing of recent Portuguese myxoma virus field isolates exhibits a high degree of genetic stability. Vet Microbiol 2010, 140: 161-166. 10.1016/j.vetmic.2009.07.028PubMedCrossRef
2.
go back to reference Marlier D, Herbots J, Detilleux J, Lemaire M, Thiry E, Vindevogel H: Cross-sectional study of the association between pathological conditions and myxoma-virus seroprevalence in intensive rabbit farms in Europe. Prev Vet Med 2001, 48: 55-64. 10.1016/S0167-5877(00)00177-XPubMedCrossRef Marlier D, Herbots J, Detilleux J, Lemaire M, Thiry E, Vindevogel H: Cross-sectional study of the association between pathological conditions and myxoma-virus seroprevalence in intensive rabbit farms in Europe. Prev Vet Med 2001, 48: 55-64. 10.1016/S0167-5877(00)00177-XPubMedCrossRef
3.
go back to reference Farsang A, Makranszki L, Dobos-Kovacs M, Virag G, Fabian K, Barna T, Kulcsar G, Kucsera L, Vetesi F: Occurrence of atypical myxomatosis in Central Europe: clinical and virological examinations. Acta Veterinaria Hungarica 2003, 51: 493-501. 10.1556/AVet.51.2003.4.7PubMedCrossRef Farsang A, Makranszki L, Dobos-Kovacs M, Virag G, Fabian K, Barna T, Kulcsar G, Kucsera L, Vetesi F: Occurrence of atypical myxomatosis in Central Europe: clinical and virological examinations. Acta Veterinaria Hungarica 2003, 51: 493-501. 10.1556/AVet.51.2003.4.7PubMedCrossRef
4.
go back to reference Kritas SK, Dovas C, Fortomaris P, Petridou E, Farsang A, Koptopoulos G: A pathogenic myxoma virus in vaccinated and non-vaccinated commercial rabbits. Res Vet Sci 2008, 85: 622-624. 10.1016/j.rvsc.2008.03.008PubMedCrossRef Kritas SK, Dovas C, Fortomaris P, Petridou E, Farsang A, Koptopoulos G: A pathogenic myxoma virus in vaccinated and non-vaccinated commercial rabbits. Res Vet Sci 2008, 85: 622-624. 10.1016/j.rvsc.2008.03.008PubMedCrossRef
5.
go back to reference Kerr PJ, Best SM: Myxoma virus in rabbits. Rev Sci Tech 1998, 17: 256-268.PubMed Kerr PJ, Best SM: Myxoma virus in rabbits. Rev Sci Tech 1998, 17: 256-268.PubMed
6.
go back to reference Saint KM, French N, Kerr P: Genetic variation in Australian isolates of myxoma virus: an evolutionary and epidemiological study. Arch Virol 2001, 146: 1105-1123. 10.1007/s007050170109PubMedCrossRef Saint KM, French N, Kerr P: Genetic variation in Australian isolates of myxoma virus: an evolutionary and epidemiological study. Arch Virol 2001, 146: 1105-1123. 10.1007/s007050170109PubMedCrossRef
7.
go back to reference Labudovic A, Perkins H, van Leeuwen B, Kerr P: Sequence mapping of the Californian MSW strain of Myxoma virus. Arch Virol 2004, 149: 553-570. 10.1007/s00705-003-0222-6PubMedCrossRef Labudovic A, Perkins H, van Leeuwen B, Kerr P: Sequence mapping of the Californian MSW strain of Myxoma virus. Arch Virol 2004, 149: 553-570. 10.1007/s00705-003-0222-6PubMedCrossRef
8.
go back to reference Morales M, Ramirez MA, Cano MJ, Parraga M, Castilla J, Perez-Ordoyo LI, Torres JM, Barcena J: Genome comparison of a nonpathogenic myxoma virus field strain with its ancestor, the virulent Lausanne strain. J Virol 2009, 83: 2397-2403. 10.1128/JVI.02189-08PubMedPubMedCentralCrossRef Morales M, Ramirez MA, Cano MJ, Parraga M, Castilla J, Perez-Ordoyo LI, Torres JM, Barcena J: Genome comparison of a nonpathogenic myxoma virus field strain with its ancestor, the virulent Lausanne strain. J Virol 2009, 83: 2397-2403. 10.1128/JVI.02189-08PubMedPubMedCentralCrossRef
9.
go back to reference Alda F, Gaitero T, Suarez M, Doadrio I: Molecular characterisation and recent evolution of myxoma virus in Spain. Arch Virol 2009, 154: 1659-1670. 10.1007/s00705-009-0494-6PubMedCrossRef Alda F, Gaitero T, Suarez M, Doadrio I: Molecular characterisation and recent evolution of myxoma virus in Spain. Arch Virol 2009, 154: 1659-1670. 10.1007/s00705-009-0494-6PubMedCrossRef
10.
go back to reference Fenner F, Marshall ID: A comparison of the virulence for European rabbits (Oryctolagus cuniculus) of strains of myxoma virus recovered in the field in Australia, Europe and America. J Hyg (Lond) 1957, 55: 149-191.CrossRef Fenner F, Marshall ID: A comparison of the virulence for European rabbits (Oryctolagus cuniculus) of strains of myxoma virus recovered in the field in Australia, Europe and America. J Hyg (Lond) 1957, 55: 149-191.CrossRef
11.
go back to reference Kerr PJ, Merchant JC, Silvers L, Hood GM, Robinson AJ: Monitoring the spread of myxoma virus in rabbit Oryctolagus cuniculus populations on the southern tablelands of New South Wales, Australia. II. Selection of a strain of virus for release. Epidemiol Infect 2003, 130: 123-133. 10.1017/S0950268802007860PubMedPubMedCentralCrossRef Kerr PJ, Merchant JC, Silvers L, Hood GM, Robinson AJ: Monitoring the spread of myxoma virus in rabbit Oryctolagus cuniculus populations on the southern tablelands of New South Wales, Australia. II. Selection of a strain of virus for release. Epidemiol Infect 2003, 130: 123-133. 10.1017/S0950268802007860PubMedPubMedCentralCrossRef
12.
go back to reference Cameron C, Hota-Mitchell S, Chen L, Barrett J, Cao JX, Macaulay C, Willer D, Evans D, McFadden G: The complete DNA sequence of myxoma virus. Virology 1999, 264: 298-318. 10.1006/viro.1999.0001PubMedCrossRef Cameron C, Hota-Mitchell S, Chen L, Barrett J, Cao JX, Macaulay C, Willer D, Evans D, McFadden G: The complete DNA sequence of myxoma virus. Virology 1999, 264: 298-318. 10.1006/viro.1999.0001PubMedCrossRef
13.
go back to reference Barcena J, Pages-Mante A, March R, Morales M, Ramirez MA, Sanchez-Vizcaino JM, Torres JM: Isolation of an attenuated myxoma virus field strain that can confer protection against myxomatosis on contacts of vaccinates. Arch Virol 2000, 145: 759-771. 10.1007/s007050050669PubMedCrossRef Barcena J, Pages-Mante A, March R, Morales M, Ramirez MA, Sanchez-Vizcaino JM, Torres JM: Isolation of an attenuated myxoma virus field strain that can confer protection against myxomatosis on contacts of vaccinates. Arch Virol 2000, 145: 759-771. 10.1007/s007050050669PubMedCrossRef
14.
go back to reference Everett H, Barry M, Lee SF, Sun X, Graham K, Stone J, Bleackley RC, McFadden G: M11L: a novel mitochondria-localized protein of myxoma virus that blocks apoptosis of infected leukocytes. J Exp Med 2000, 191: 1487-1498. 10.1084/jem.191.9.1487PubMedPubMedCentralCrossRef Everett H, Barry M, Lee SF, Sun X, Graham K, Stone J, Bleackley RC, McFadden G: M11L: a novel mitochondria-localized protein of myxoma virus that blocks apoptosis of infected leukocytes. J Exp Med 2000, 191: 1487-1498. 10.1084/jem.191.9.1487PubMedPubMedCentralCrossRef
15.
go back to reference Wang G, Barrett JW, Nazarian SH, Everett H, Gao X, Bleackley C, Colwill K, Moran MF, McFadden G: Myxoma virus M11L prevents apoptosis through constitutive interaction with Bak. J Virol 2004, 78: 7097-7111. 10.1128/JVI.78.13.7097-7111.2004PubMedPubMedCentralCrossRef Wang G, Barrett JW, Nazarian SH, Everett H, Gao X, Bleackley C, Colwill K, Moran MF, McFadden G: Myxoma virus M11L prevents apoptosis through constitutive interaction with Bak. J Virol 2004, 78: 7097-7111. 10.1128/JVI.78.13.7097-7111.2004PubMedPubMedCentralCrossRef
16.
go back to reference Cameron CM, Barrett JW, Liu L, Lucas AR, McFadden G: Myxoma virus M141R expresses a viral CD200 (vOX-2) that is responsible for down-regulation of macrophage and T-cell activation in vivo. J Virol 2005, 79: 6052-6067. 10.1128/JVI.79.10.6052-6067.2005PubMedPubMedCentralCrossRef Cameron CM, Barrett JW, Liu L, Lucas AR, McFadden G: Myxoma virus M141R expresses a viral CD200 (vOX-2) that is responsible for down-regulation of macrophage and T-cell activation in vivo. J Virol 2005, 79: 6052-6067. 10.1128/JVI.79.10.6052-6067.2005PubMedPubMedCentralCrossRef
17.
go back to reference Duteyrat JL, Gelfi J, Bertagnoli S: Ultrastructural study of myxoma virus morphogenesis. Arch Virol 2006, 151: 2161-2180. 10.1007/s00705-006-0791-2PubMedCrossRef Duteyrat JL, Gelfi J, Bertagnoli S: Ultrastructural study of myxoma virus morphogenesis. Arch Virol 2006, 151: 2161-2180. 10.1007/s00705-006-0791-2PubMedCrossRef
18.
go back to reference Su J, Wang G, Barrett JW, Irvine TS, Gao X, McFadden G: Myxoma virus M11L blocks apoptosis through inhibition of conformational activation of Bax at the mitochondria. J Virol 2006, 80: 1140-1151. 10.1128/JVI.80.3.1140-1151.2006PubMedPubMedCentralCrossRef Su J, Wang G, Barrett JW, Irvine TS, Gao X, McFadden G: Myxoma virus M11L blocks apoptosis through inhibition of conformational activation of Bax at the mitochondria. J Virol 2006, 80: 1140-1151. 10.1128/JVI.80.3.1140-1151.2006PubMedPubMedCentralCrossRef
19.
go back to reference Barrett JW, Sypula J, Wang F, Alston LR, Shao Z, Gao X, Irvine TS, McFadden G: M135R is a novel cell surface virulence factor of myxoma virus. J Virol 2007, 81: 106-114. 10.1128/JVI.01633-06PubMedPubMedCentralCrossRef Barrett JW, Sypula J, Wang F, Alston LR, Shao Z, Gao X, Irvine TS, McFadden G: M135R is a novel cell surface virulence factor of myxoma virus. J Virol 2007, 81: 106-114. 10.1128/JVI.01633-06PubMedPubMedCentralCrossRef
20.
go back to reference Adams MM, van Leeuwen BH, Kerr PJ: Construction and evaluation of live attenuated myxoma virus vaccines with targeted virulence gene deletions. Vaccine 2008, 26: 5843-5854. 10.1016/j.vaccine.2008.08.036PubMedCrossRef Adams MM, van Leeuwen BH, Kerr PJ: Construction and evaluation of live attenuated myxoma virus vaccines with targeted virulence gene deletions. Vaccine 2008, 26: 5843-5854. 10.1016/j.vaccine.2008.08.036PubMedCrossRef
21.
go back to reference Barrett JW, Werden SJ, Wang F, McKillop WM, Jimenez J, Villeneuve D, McFadden G, Dekaban GA: Myxoma virus M130R is a novel virulence factor required for lethal myxomatosis in rabbits. Virus Res 2009, 144: 258-265. 10.1016/j.virusres.2009.05.009PubMedCrossRef Barrett JW, Werden SJ, Wang F, McKillop WM, Jimenez J, Villeneuve D, McFadden G, Dekaban GA: Myxoma virus M130R is a novel virulence factor required for lethal myxomatosis in rabbits. Virus Res 2009, 144: 258-265. 10.1016/j.virusres.2009.05.009PubMedCrossRef
22.
go back to reference Opgenorth A, Graham K, Nation N, Strayer D, McFadden G: Deletion analysis of two tandemly arranged virulence genes in myxoma virus, M11L and myxoma growth factor. J Virol 1992,66(8):4720-31.PubMedPubMedCentral Opgenorth A, Graham K, Nation N, Strayer D, McFadden G: Deletion analysis of two tandemly arranged virulence genes in myxoma virus, M11L and myxoma growth factor. J Virol 1992,66(8):4720-31.PubMedPubMedCentral
23.
go back to reference Blanié S, Mortier J, Delverdier M, Bertagnoli S, Camus-Bouclainville C: M148R and M149R are two virulence factors for myxoma virus pathogenesis in the European rabbit. Vet Res 2009, 40: 11. Epub 2008 Nov 19 10.1051/vetres:2008049PubMedPubMedCentralCrossRef Blanié S, Mortier J, Delverdier M, Bertagnoli S, Camus-Bouclainville C: M148R and M149R are two virulence factors for myxoma virus pathogenesis in the European rabbit. Vet Res 2009, 40: 11. Epub 2008 Nov 19 10.1051/vetres:2008049PubMedPubMedCentralCrossRef
24.
go back to reference Dalton KP, Ringleb F, Martin Alonso JM, Parra F: Rapid identification of myxoma virus variants by long-range PCR and restriction fragment length polymorphism analysis. J Virol Methods 2009, 161: 284-288. 10.1016/j.jviromet.2009.06.026PubMedCrossRef Dalton KP, Ringleb F, Martin Alonso JM, Parra F: Rapid identification of myxoma virus variants by long-range PCR and restriction fragment length polymorphism analysis. J Virol Methods 2009, 161: 284-288. 10.1016/j.jviromet.2009.06.026PubMedCrossRef
25.
go back to reference Fenner F, Poole WE, Marshall ID, Dyce AL: Studies in the epidemiology of infectious myxomatosis of rabbits. VI. The experimental introduction of the European strain of myxoma virus into Australian wild rabbit populations. J Hyg (Lond) 1957, 55: 192-206.CrossRef Fenner F, Poole WE, Marshall ID, Dyce AL: Studies in the epidemiology of infectious myxomatosis of rabbits. VI. The experimental introduction of the European strain of myxoma virus into Australian wild rabbit populations. J Hyg (Lond) 1957, 55: 192-206.CrossRef
26.
go back to reference Best SM, Kerr PJ: Coevolution of host and virus: the pathogenesis of virulent and attenuated strains of myxoma virus in resistant and susceptible European rabbits. Virology 2000, 267: 36-48. 10.1006/viro.1999.0104PubMedCrossRef Best SM, Kerr PJ: Coevolution of host and virus: the pathogenesis of virulent and attenuated strains of myxoma virus in resistant and susceptible European rabbits. Virology 2000, 267: 36-48. 10.1006/viro.1999.0104PubMedCrossRef
27.
go back to reference Delibes-Mateos M, Ramírez E, Ferreras P, Villafuerte R: Translocations as a risk for the conservation of European wild rabbit Oryctolagus cuniculus lineages. Oryx 2008, 42: 259-264. 10.1017/S0030605308006984CrossRef Delibes-Mateos M, Ramírez E, Ferreras P, Villafuerte R: Translocations as a risk for the conservation of European wild rabbit Oryctolagus cuniculus lineages. Oryx 2008, 42: 259-264. 10.1017/S0030605308006984CrossRef
28.
go back to reference Upton C, Macen JL, Schreiber M, McFadden G: Myxoma virus expresses a secreted protein with homology to the tumor necrosis factor receptor gene family that contributes to viral virulence. Virology 1991, 184: 370-382. 10.1016/0042-6822(91)90853-4PubMedCrossRef Upton C, Macen JL, Schreiber M, McFadden G: Myxoma virus expresses a secreted protein with homology to the tumor necrosis factor receptor gene family that contributes to viral virulence. Virology 1991, 184: 370-382. 10.1016/0042-6822(91)90853-4PubMedCrossRef
29.
go back to reference Zuniga MC: A pox on thee! Manipulation of the host immune system by myxoma virus and implications for viral-host co-adaptation. Virus Res 2002, 88: 17-33. 10.1016/S0168-1702(02)00118-1PubMedCrossRef Zuniga MC: A pox on thee! Manipulation of the host immune system by myxoma virus and implications for viral-host co-adaptation. Virus Res 2002, 88: 17-33. 10.1016/S0168-1702(02)00118-1PubMedCrossRef
30.
go back to reference Villafuerte R, Viñuela J, Blanc JC: Extensive predator persecution caused by population crash in a game species: The case of red kites and rabbits in Spain. Biological conservation 1998, 84: 181-188. 10.1016/S0006-3207(97)00094-3CrossRef Villafuerte R, Viñuela J, Blanc JC: Extensive predator persecution caused by population crash in a game species: The case of red kites and rabbits in Spain. Biological conservation 1998, 84: 181-188. 10.1016/S0006-3207(97)00094-3CrossRef
31.
go back to reference Dalton KP, Ringleb F, Martin Alonso JM, Parra F: Rapid purification of myxoma virus DNA. J Virol Methods 2009, 162: 284-287. 10.1016/j.jviromet.2009.08.003PubMedCrossRef Dalton KP, Ringleb F, Martin Alonso JM, Parra F: Rapid purification of myxoma virus DNA. J Virol Methods 2009, 162: 284-287. 10.1016/j.jviromet.2009.08.003PubMedCrossRef
Metadata
Title
Molecular characterisation of virulence graded field isolates of myxoma virus
Authors
Kevin P Dalton
Ines Nicieza
Aroa Baragaño
Jose Manuel Martín Alonso
Francisco Parra
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2010
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/1743-422X-7-49

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