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Viruses  2013 

Expanding Possibilities for Intervention against Small Ruminant Lentiviruses through Genetic Marker-Assisted Selective Breeding

DOI: 10.3390/v5061466

Keywords: small ruminant lentivirus, susceptibility, marker-assisted selection, sheep, goats, TMEM154

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Small ruminant lentiviruses include members that infect sheep (ovine lentivirus [OvLV]; also known as ovine progressive pneumonia virus/maedi-visna virus) and goats (caprine arthritis encephalitis virus [CAEV]). Breed differences in seroprevalence and proviral concentration of OvLV had suggested a strong genetic component in susceptibility to infection by OvLV in sheep. A genetic marker test for susceptibility to OvLV has been developed recently based on the TMEM154 gene with validation data from over 2,800 sheep representing nine cohorts. While no single genotype has been shown to have complete resistance to OvLV, consistent association in thousands of sheep from multiple breeds and management conditions highlight a new strategy for intervention by selective breeding. This genetic marker-assisted selection (MAS) has the potential to be a useful addition to existing viral control measures. Further, the discovery of multiple additional genomic regions associated with susceptibility to or control of OvLV suggests that additional genetic marker tests may be developed to extend the reach of MAS in the future. This review will cover the strengths and limitations of existing data from host genetics as an intervention and outline additional questions for future genetic research in sheep, goats, small ruminant lentiviruses, and their host-pathogen interactions.


[1]  Thormar, H. Maedi-visna virus and its relationship to human immunodeficiency virus. AIDS Rev. 2005, 7, 233–245.
[2]  Leroux, C.; Cruz, J.C.; Mornex, J.F. SRLVs: A genetic continuum of lentiviral species in sheep and goats with cumulative evidence of cross species transmission. Curr. HIV Res. 2010, 8, 94–100, doi:10.2174/157016210790416415.
[3]  Blacklaws, B.A. Small ruminant lentiviruses: Immunopathogenesis of visna-maedi and caprine arthritis and encephalitis virus. Comp. Immunol. Microbiol. Infect. Dis. 2012, 35, 259–269, doi:10.1016/j.cimid.2011.12.003.
[4]  Rowe, J.D.; East, N.E. Risk factors for transmission and methods for control of caprine arthritis-encephalitis virus infection. Vet. Clin. North Am. Food Anim. Pract. 1997, 13, 35–53.
[5]  Banks, K.; Adams, D.; McGuire, T.; Carlson, J. Experimental infection of sheep by caprine arthritis-encephalitis virus and goats by progressive pneumonia virus. Am. J. Vet. Res. 1983, 44, 2307–2311.
[6]  Shah, C.; Huder, J.B.; Boni, J.; Schonmann, M.; Muhlherr, J.; Lutz, H.; Schupbach, J. Direct evidence for natural transmission of small-ruminant lentiviruses of subtype a4 from goats to sheep and vice versa. J. Virol. 2004, 78, 7518–7522, doi:10.1128/JVI.78.14.7518-7522.2004.
[7]  Hai-qing, Y.; Ahemat, D.; Li, B.; Hui, Z.; Li-chun, Q. Pathological observation of Xinjiang karakul sheep naturally infected with maedi-visna virus. Prog. Vet. Med. 2006, 2, 75–78.
[8]  Vorster, J.; Dungu, B.; Marais, L.; York, D.; Williams, R.; Boshoff, C. A perspective on maedi-visna in South Africa. J. S. Afr. Vet. Assoc. 1996, 67, 2–3.
[9]  Kitching, R. The Economic Significance and Control of Small Ruminant Viruses in North Africa and West Asia. In Increasing Small Ruminant Productivity in Semi-Arid Areas; Thomson, E.F., Thomson, F.S., Eds.; Springer Netherlands: Dordrecht, The Netherlands, 1988; Volume 47, pp. 225–236.
[10]  Ravazzolo, A.P.; Reischak, D.; Peterhans, E.; Zanoni, R. Phylogenetic analysis of small ruminant lentiviruses from southern Brazil. Virus Res. 2001, 79, 117–123, doi:10.1016/S0168-1702(01)00339-2.
[11]  Snyder, S.; DeMartini, J.; Ameghino, E.; Caletti, E. Coexistence of pulmonary adenomatosis and progressive pneumonia in sheep in the central sierra of Peru. Am. J. Vet. Res. 1983, 44, 1334–1338.
[12]  Reina, R.; Berriatua, E.; Lujan, L.; Juste, R.; Sanchez, A.; de Andres, D.; Amorena, B. Prevention strategies against small ruminant lentiviruses: An update. Vet. J. 2009, 182, 31–37, doi:10.1016/j.tvjl.2008.05.008.
[13]  Torsteinsdottir, S.; Andresdottir, V.; Arnarson, H.; Petursson, G. Immune response to maedi-visna virus. Front. Biosci. 2007, 12, 1532–1543, doi:10.2741/2166.
[14]  Bertolotti, L.; Reina, R.; Mazzei, M.; Preziuso, S.; Camero, M.; Carrozza, M.L.; Cavalli, A.; Juganaru, M.; Profiti, M.; De Meneghi, D.; et al. Small ruminant lentivirus genotype B and E interaction: Evidences on the role of Roccaverano strain on reducing proviral load of the challenging CAEV strain. Vet. Microbiol. 2012, 163, 33–41.
[15]  Narayan, O.; Kennedy-Stoskopf, S.; Zink, M.C. Lentivirus-host interactions: Lessons from visna and caprine arthritis-encephalitis viruses. Ann. Neurol. 1988, 23, S95–S100, doi:10.1002/ana.410230725.
[16]  Arsenault, J.; Dubreuil, P.; Girard, C.; Simard, C.; Belanger, D. Maedi-visna impact on productivity in Quebec sheep flocks (Canada). Prev. Vet. Med. 2003, 59, 125–137, doi:10.1016/S0167-5877(03)00086-2.
[17]  Keen, J.E.; Hungerford, L.L.; Littledike, E.T.; Wittum, T.E.; Kwang, J. Effect of ewe ovine lentivirus infection on ewe and lamb productivity. Prev. Vet. Med. 1997, 30, 155–169, doi:10.1016/S0167-5877(96)01101-4.
[18]  Peterhans, E.; Greenland, T.; Badiola, J.; Harkiss, G.; Bertoni, G.; Amorena, B.; Eliaszewicz, M.; Juste, R.A.; Krassnig, R.; Lafont, J.P.; et al. Routes of transmission and consequences of small ruminant lentiviruses (SRLVs) infection and eradication schemes. Vet. Res. 2004, 35, 257–274, doi:10.1051/vetres:2004014.
[19]  Bennett, R. The ‘direct costs’ of livestock disease: The development of a system of models for the analysis of 30 endemic livestock diseases in Great Britain. J. Agric. Econ. 2003, 54, 55–71.
[20]  Bennett, R.; IJpelaar, J. Updated estimates of the costs associated with thirty four endemic livestock diseases in Great Britain: A note. J. Agric. Econ. 2005, 56, 135–144, doi:10.1111/j.1477-9552.2005.tb00126.x.
[21]  McGuire, T.C.; O'Rourke, K.I.; Knowles, D.P.; Cheevers, W.P. Caprine arthritis encephalitis lentivirus transmission and disease. Curr. Top. Microbiol. Immunol. 1990, 160, 61–75, doi:10.1007/978-3-642-75267-4_4.
[22]  Martínez-Navalón, B.; Peris, C.; Gómez, E.A.; Peris, B.; Roche, M.L.; Caballero, C.; Goyena, E.; Berriatua, E. Quantitative estimation of the impact of caprine arthritis encephalitis virus infection on milk production by dairy goats. Vet. J. 2013. in press. Available online: (accessed on 13 June 2013).
[23]  Leitner, G.; Krifucks, O.; Weisblit, L.; Lavi, Y.; Bernstein, S.; Merin, U. The effect of caprine arthritis encephalitis virus infection on production in goats. Vet. J. 2010, 183, 328–331, doi:10.1016/j.tvjl.2008.12.001.
[24]  Kaba, J.; Strzalkowska, N.; Jozwik, A.; Krzyzewski, J.; Bagnicka, E. Twelve-year cohort study on the influence of caprine arthritis-encephalitis virus infection on milk yield and composition. J. Dairy Sci. 2012, 95, 1617–1622, doi:10.3168/jds.2011-4680.
[25]  Smith, M.; Cutlip, R. Effects of infection with caprine arthritis-encephalitis virus on milk production in goats. J. Am. Vet. Med. Assoc. 1988, 193, 63–67.
[26]  Gates, N.L.; Winward, L.D.; Gorham, J.R.; Shen, D.T. Serologic survey of prevalence of ovine progressive pneumonia in Idaho range sheep. J. Am. Vet. Med. Assoc. 1978, 173, 1575–1577.
[27]  Houwers, D.J.; Visscher, A.H.; Defize, P.R. Importance of ewe/lamb relationship and breed in the epidemiology of maedi-visna virus infections. Res. Vet. Sci. 1989, 46, 5–8.
[28]  Snowder, G.D.; Gates, N.L.; Glimp, H.A.; Gorham, J.R. Prevalence and effect of subclinical ovine progressive pneumonia virus infection on ewe wool and lamb production. J. Am. Vet. Med. Assoc. 1990, 197, 475–479.
[29]  Keen, J.E.; Hungerford, L.L.; Wittum, T.E.; Kwang, J.; Littledike, E.T. Risk factors for seroprevalence of ovine lentivirus in breeding ewe flocks in Nebraska, USA. Prev. Vet. Med. 1997, 30, 81–94, doi:10.1016/S0167-5877(96)01121-X.
[30]  Vitu, C.; Russo, P. Caprine enzootic arthritis-encephalitis in france: Epidemiological and experimental studies. Comp. Immunol. Microbiol. Infect. Dis. 1988, 11, 27–34, doi:10.1016/0147-9571(88)90005-7.
[31]  Grewal, A.S.; Greenwood, P.E.; Burton, R.W.; Smith, J.E.; Batty, E.M.; North, R. Caprine retrovirus infection in new south wales: Virus isolations, clinical and histopathological findings and prevalence of antibody. Aust. Vet. J. 1986, 63, 245–248, doi:10.1111/j.1751-0813.1986.tb02985.x.
[32]  Rowe, J.D.; East, N.E.; Franti, C.E.; Thurmond, M.C.; Pedersen, N.C.; Theilen, G.H. Risk factors associated with the incidence of seroconversion to caprine arthritis-encephalitis virus in goats on california dairies. Am. J. Vet. Res. 1992, 53, 2396–2403.
[33]  Cutlip, R.C.; Lehmkuhl, H.D.; Sacks, J.M.; Weaver, A.L. Prevalence of antibody to caprine arthritis-encephalitis virus in goats in the United States. J. Am. Vet. Med. Assoc. 1992, 200, 802–805.
[34]  Herrmann-Hoesing, L.M.; White, S.N.; Mousel, M.R.; Lewis, G.S.; Knowles, D.P. Ovine progressive pneumonia provirus levels associate with breed and Ovar-DRB1. Immunogenetics 2008, 60, 749–758, doi:10.1007/s00251-008-0328-9.
[35]  Berriatua, E.; Alvarez, V.; Extramiana, B.; Gonzalez, L.; Daltabuit, M.; Juste, R. Transmission and control implications of seroconversion to maedi-visna virus in basque dairy-sheep flocks. Prev. Vet. Med. 2003, 60, 265–279, doi:10.1016/S0167-5877(03)00163-6.
[36]  De la Concha-Bermejillo, A.; Brodie, S.J.; Magnus-Corral, S.; Bowen, R.A.; DeMartini, J.C. Pathologic and serologic responses of isogeneic twin lambs to phenotypically distinct lentiviruses. J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. 1995, 8, 116–123.
[37]  Ruff, G.; Lazary, S. Evidence for linkage between the caprine leucocyte antigen (CLA) system and susceptibility to CAE virus-induced arthritis in goats. Immunogenetics 1988, 28, 303–309, doi:10.1007/BF00364227.
[38]  Ruff, G.; Regli, J.; Lazary, S. Occurrence of caprine leucocyte class I and II antigens in Saanen goats affected by caprine arthritis (CAE). Int. J. Immunogenet. 1993, 20, 285–288, doi:10.1111/j.1744-313X.1993.tb00144.x.
[39]  Dolf, G.; Ruff, G. A DNA fingerprinting band associated with the susceptibility to CAE virus-induced arthritis in goats. Br. Vet. J. 1994, 150, 349–353, doi:10.1016/S0007-1935(05)80151-4.
[40]  Houwers, D.J.; Schaake, J., Jr.; de Boer, G.F. Maedi-visna control in sheep. II. Half-yearly serological testing with culling of positive ewes and progeny. Vet. Microbiol. 1984, 9, 445–451.
[41]  Houwers, D.J.; Konig, C.D.; de Boer, G.F.; Schaake, J., Jr. Maedi-visna control in sheep. I. Artificial rearing of colostrum-deprived lambs. Vet. Microbiol. 1983, 8, 179–185.
[42]  Cross, R.; Smith, C.; Moorhead, P. Vertical transmission of progressive pneumonia of sheep. Am. J. Vet. Res. 1975, 36, 465–468.
[43]  Cutlip, R.C.; Lehmkuhl, H.D.; Jackson, T.A. Intrauterine transmission of ovine progressive pneumonia virus. Am. J. Vet. Res. 1981, 42, 1795–1797.
[44]  Houwers, D.J.; Konig, C.D.; Bakker, J.; de Boer, M.J.; Pekelder, J.J.; Sol, J.; Vellema, P.; de Vries, G. Maedi-visna control in sheep. III: Results and evaluation of a voluntary control program in the netherlands over a period of four years. Vet. Quart. 1987, 9, 29S–36S, doi:10.1080/01652176.1987.9694136.
[45]  Leginagoikoa, I.; Juste, R.A.; Barandika, J.; Amorena, B.; de Andres, D.; Lujan, L.; Badiola, J.; Berriatua, E. Extensive rearing hinders Maedi-Visna Virus (MVV) infection in sheep. Vet. Res. 2006, 37, 767–778, doi:10.1051/vetres:2006034.
[46]  Leginagoikoa, I.; Minguijon, E.; Juste, R.A.; Barandika, J.; Amorena, B.; de Andres, D.; Badiola, J.J.; Lujan, L.; Berriatua, E. Effects of housing on the incidence of visna/maedi virus infection in sheep flocks. Res. Vet. Sci. 2010, 88, 415–421, doi:10.1016/j.rvsc.2009.11.006.
[47]  Lago, N.; Lopez, C.; Panadero, R.; Cienfuegos, S.; Pato, J.; Prieto, A.; Diaz, P.; Mourazos, N.; Fernandez, G. Seroprevalence and risk factors associated with visna/maedi virus in semi-intensive lamb-producing flocks in northwestern spain. Prev. Vet. Med. 2012, 103, 163–169, doi:10.1016/j.prevetmed.2011.09.019.
[48]  Kwong, P.D.; Mascola, J.R.; Nabel, G.J. The changing face of HIV vaccine research. J. Int. AIDS Soc. 2012, 15, e17407.
[49]  Olender, S.; Wilkin, T.J.; Taylor, B.S.; Hammer, S.M. Advances in antiretroviral therapy. Top. Antivir. Med. 2012, 20, 61–86.
[50]  Synge, B.; Ritchie, C. Elimination of small ruminant lentivirus infection from sheep flocks and goat herds aided by health schemes in Great Britain. Vet. Rec. 2010, 167, 739–743, doi:10.1136/vr.c5853.
[51]  Houwers, D.J. Economic importance, epidemiology and control. In Maedi-Visna and Related Diseases; Springer US: New York, NY, USA, 1990; pp. 83–117.
[52]  Williams, J.L. The use of marker-assisted selection in animal breeding and biotechnology. Rev. Sci. Tech. 2005, 24, 379–391.
[53]  Dekkers, J.C. Commercial application of marker- and gene-assisted selection in livestock: Strategies and lessons. J. Anim. Sci. 2004, 82, E313–E328.
[54]  Anderson, R.M.; May, R.M. Infectious Diseases of Humans: Dynamics and Control; Oxford University Press: New York, NY, USA, 1992; p. 768.
[55]  Woolhouse, M.E.; Dye, C.; Etard, J.F.; Smith, T.; Charlwood, J.D.; Garnett, G.P.; Hagan, P.; Hii, J.L.; Ndhlovu, P.D.; Quinnell, R.J.; et al. Heterogeneities in the transmission of infectious agents: Implications for the design of control programs. Proc. Natl. Acad. Sci. USA 1997, 94, 338–342, doi:10.1073/pnas.94.1.338.
[56]  Lloyd-Smith, J.O.; Schreiber, S.J.; Kopp, P.E.; Getz, W.M. Superspreading and the effect of individual variation on disease emergence. Nature 2005, 438, 355–359, doi:10.1038/nature04153.
[57]  Galvani, A.P.; May, R.M. Epidemiology: Dimensions of superspreading. Nature 2005, 438, 293–295, doi:10.1038/438293a.
[58]  Smith, D.L.; Dushoff, J.; Snow, R.W.; Hay, S.I. The entomological inoculation rate and plasmodium falciparum infection in African children. Nature 2005, 438, 492–495, doi:10.1038/nature04024.
[59]  Galvani, A.P. Immunity, antigenic heterogeneity, and aggregation of helminth parasites. J. Parasitol. 2003, 89, 232–241, doi:10.1645/0022-3395(2003)089[0232:IAHAAO]2.0.CO;2.
[60]  May, R.M.; Anderson, R.M. Transmission dynamics of HIV infection. Nature 1987, 326, 137–142, doi:10.1038/326137a0.
[61]  Bauch, C.T.; Lloyd-Smith, J.O.; Coffee, M.P.; Galvani, A.P. Dynamically modeling sars and other newly emerging respiratory illnesses: Past, present, and future. Epidemiology 2005, 16, 791–801, doi:10.1097/01.ede.0000181633.80269.4c.
[62]  Perez, M.; Biescas, E.; de Andres, X.; Leginagoikoa, I.; Salazar, E.; Berriatua, E.; Reina, R.; Bolea, R.; de Andres, D.; Juste, R.A.; et al. Visna/maedi virus serology in sheep: Survey, risk factors and implementation of a successful control programme in Aragon (Spain). Vet. J. 2010, 186, 221–225, doi:10.1016/j.tvjl.2009.07.031.
[63]  Zanoni, R.; Pauli, U.; Peterhans, E. Detection of caprine arthritis-encephalitis- and maedi-visna viruses using the polymerase chain reaction. Experientia 1990, 46, 316–319, doi:10.1007/BF01951776.
[64]  Barlough, J.; East, N.; Rowe, J.D.; van Hoosear, K.; DeRock, E.; Bigornia, L.; Rimstad, E. Double-nested polymerase chain reaction for detection of caprine arthritis-encephalitis virus proviral DNA in blood, milk, and tissues of infected goats. J. Virol. Methods 1994, 50, 101–113.
[65]  Ding, E. Analysis and PCR detection of antigen compositions of ovine progressive pneumonia virus. Sci. China B 1995, 38, 573–579.
[66]  Sanna, E.; Sanna, M.P.; Vitali, C.G.; Renzoni, G.; Sanna, L.; Spano, S.; Rossi, G.; Leoni, A. Proviral DNA in the brains of goats infected with caprine arthritis-encephalitis virus. J. Comp. Pathol. 1999, 121, 271–276.
[67]  Celer, V., Jr.; Celer, V.; Nejedla, E.; Bertoni, G.; Peterhans, E.; Zanoni, R.G. The detection of proviral DNA by semi-nested polymerase chain reaction and phylogenetic analysis of Czech maedi-visna isolates based on gag gene sequences. J. Vet. Med. B Infect. Dis. Vet. Public Health 2000, 47, 203–215, doi:10.1046/j.1439-0450.2000.00330.x.
[68]  Fieni, F.; Rowe, J.; van Hoosear, K.; Burucoa, C.; Oppenheim, S.; Anderson, G.; Murray, J.; BonDurant, R. Presence of caprine arthritis-encephalitis virus (CAEV) proviral DNA in genital tract tissues of superovulated dairy goat does. Theriogenology 2003, 59, 1515–1523, doi:10.1016/S0093-691X(02)01194-9.
[69]  Ali Al Ahmad, M.Z.; Fieni, F.; Martignat, L.; Chatagnon, G.; Baril, G.; Bouvier, F.; Chebloune, Y. Proviral DNA of caprine arthritis encephalitis virus (CAEV) is detected in cumulus oophorus cells but not in oocytes from naturally infected goats. Theriogenology 2005, 64, 1656–1666, doi:10.1016/j.theriogenology.2005.04.005.
[70]  Cortez Romero, C.; Fieni, F.; Roux, C.; Russo, P.; Guibert, J.M.; Guiguen, F.; Chebloune, Y.; Pepin, M.; Pellerin, J.L. Detection of ovine lentivirus in the cumulus cells, but not in the oocytes or follicular fluid, of naturally infected sheep. Theriogenology 2006, 66, 1131–1139, doi:10.1016/j.theriogenology.2006.03.008.
[71]  Gil, A.; Rola, M.; Kuzmak, J. Application of PCR technique in diagnosis of small ruminant lentivirus infection in sheep and goats. Pol. J. Vet. Sci. 2006, 9, 213–217.
[72]  Eltahir, Y.M.; Dovas, C.I.; Papanastassopoulou, M.; Koumbati, M.; Giadinis, N.; Verghese-Nikolakaki, S.; Koptopoulos, G. Development of a semi-nested PCR using degenerate primers for the generic detection of small ruminant lentivirus proviral DNA. J. Virol. Methods 2006, 135, 240–246, doi:10.1016/j.jviromet.2006.03.010.
[73]  Herrmann-Hoesing, L.M.; White, S.N.; Lewis, G.S.; Mousel, M.R.; Knowles, D.P. Development and validation of an ovine progressive pneumonia virus quantitative PCR. Clin. Vaccine Immunol. 2007, 14, 1274–1278, doi:10.1128/CVI.00095-07.
[74]  White, S.N.; Mousel, M.R.; Reynolds, J.O.; Lewis, G.S.; Herrmann-Hoesing, L.M. Common promoter deletion is associated with 3.9-fold differential transcription of ovine CCR5 and reduced proviral level of ovine progressive pneumonia virus. Anim. Genet. 2009, 40, 583–589, doi:10.1111/j.1365-2052.2009.01882.x.
[75]  Heaton, M.P.; Clawson, M.L.; Chitko-McKown, C.G.; Leymaster, K.A.; Smith, T.P.; Harhay, G.P.; White, S.N.; Herrmann-Hoesing, L.M.; Mousel, M.R.; Lewis, G.S.; et al. Reduced lentivirus susceptibility in sheep with TMEM154 mutations. PLoS Genet. 2012, 8, e1002467, doi:10.1371/journal.pgen.1002467.
[76]  Mikula, I.; Bhide, M.; Pastorekova, S. Characterization of ovine TLR7 and TLR8 protein coding regions, detection of mutations and maedi visna virus infection. Vet. Immunol. Immunopathol. 2010, 138, 51–59, doi:10.1016/j.vetimm.2010.06.015.
[77]  White, S.N.; Mousel, M.R.; Herrmann-Hoesing, L.M.; Reynolds, J.O.; Leymaster, K.A.; Neibergs, H.L.; Lewis, G.S.; Knowles, D.P. Genome-wide association identifies multiple genomic regions associated with susceptibility to and control of ovine lentivirus. PLoS One 2012, 7, e47829.
[78]  Mikula, I., Jr.; Mikula, I., Sr. Characterization of ovine toll-like receptor 9 protein coding region, comparative analysis, detection of mutations and maedi visna infection. Dev. Comp. Immunol. 2011, 35, 182–192.
[79]  Zhang, Z.; Watt, N.J.; Hopkins, J.; Harkiss, G.; Woodall, C.J. Quantitative analysis of maedi-visna virus DNA load in peripheral blood monocytes and alveolar macrophages. J. Virol. Methods 2000, 86, 13–20.
[80]  Carrozza, M.L.; Mazzei, M.; Bandecchi, P.; Fraisier, C.; Perez, M.; Suzan-Monti, M.; de Andres, D.; Amorena, B.; Rosati, S.; Andresdottir, V.; et al. Development and comparison of strain specific gag and pol real-time PCR assays for the detection of visna/maedi virus. J. Virol. Methods 2010, 165, 161–167, doi:10.1016/j.jviromet.2010.01.013.
[81]  Ravazzolo, A.P.; Nenci, C.; Vogt, H.R.; Waldvogel, A.; Obexer-Ruff, G.; Peterhans, E.; Bertoni, G. Viral load, organ distribution, histopathological lesions, and cytokine mRNA expression in goats infected with a molecular clone of the caprine arthritis encephalitis virus. Virology 2006, 350, 116–127, doi:10.1016/j.virol.2006.02.014.
[82]  Brajon, G.; Mandas, D.; Liciardi, M.; Taccori, F.; Meloni, M.; Corrias, F.; Montaldo, C.; Coghe, F.; Casciari, C.; Giammarioli, M.; et al. Development and field testing of a real-time PCR assay for caprine arthritis-encephalitis-virus (CAEV). Open Virol. J. 2012, 6, 82–90, doi:10.2174/1874357901206010082.
[83]  Herrmann-Hoesing, L.M.; Noh, S.M.; White, S.N.; Snekvik, K.R.; Truscott, T.; Knowles, D.P. Peripheral ovine progressive pneumonia provirus levels correlate with and predict histological tissue lesion severity in naturally infected sheep. Clin. Vaccine Immunol. 2009, 16, 551–557, doi:10.1128/CVI.00459-08.
[84]  Larruskain, A.; Minguijon, E.; Garcia-Etxebarria, K.; Moreno, B.; Arostegui, I.; Juste, R.A.; Jugo, B.M. MHC class II DRB1 gene polymorphism in the pathogenesis of Maedi-Visna and pulmonary adenocarcinoma viral diseases in sheep. Immunogenetics 2010, 62, 75–83, doi:10.1007/s00251-009-0419-2.
[85]  Larruskain, A.; Minguijon, E.; Arostegui, I.; Moreno, B.; Juste, R.A.; Jugo, B.M. Microsatellites in immune-relevant regions and their associations with maedi-visna and ovine pulmonary adenocarcinoma viral diseases. Vet. Immunol. Immunopathol. 2012, 145, 438–446, doi:10.1016/j.vetimm.2011.12.020.
[86]  Harrington, R.D.; Herrmann-Hoesing, L.M.; White, S.N.; O'Rourke, K.I.; Knowles, D.P. Ovine progressive pneumonia provirus levels are unaffected by the prion 171r allele in an Idaho sheep flock. Genet. Sel. Evol. 2009, 41, 17, doi:10.1186/1297-9686-41-17.
[87]  Perez-Enciso, M.; Ferretti, L. Massive parallel sequencing in animal genetics: Wherefroms and wheretos. Anim. Genet. 2010, 41, 561–569, doi:10.1111/j.1365-2052.2010.02057.x.
[88]  Lenstra, J.A.; Groeneveld, L.F.; Eding, H.; Kantanen, J.; Williams, J.L.; Taberlet, P.; Nicolazzi, E.L.; Solkner, J.; Simianer, H.; Ciani, E.; et al. Molecular tools and analytical approaches for the characterization of farm animal genetic diversity. Anim. Genet. 2012, 43, 483–502, doi:10.1111/j.1365-2052.2011.02309.x.
[89]  Clop, A.; Marcq, F.; Takeda, H.; Pirottin, D.; Tordoir, X.; Bibe, B.; Bouix, J.; Caiment, F.; Elsen, J.M.; Eychenne, F.; et al. A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep. Nat. Genet. 2006, 38, 813–818, doi:10.1038/ng1810.
[90]  Andersson, L. Genetic dissection of phenotypic diversity in farm animals. Nat. Rev. Genet. 2001, 2, 130–138, doi:10.1038/35052563.
[91]  Soller, M.; Andersson, L. Genomic approaches to the improvement of disease resistance in farm animals. Rev. Sci. Tech. 1998, 17, 329–345.
[92]  Xu, J.; Wiesch, D.G.; Meyers, D.A. Genetics of complex human diseases: Genome screening, association studies and fine mapping. Clin. Exp. Allergy 1998, 28, 1–5; discussion 26–28.
[93]  Stear, M.J.; Bishop, S.C.; Mallard, B.A.; Raadsma, H. The sustainability, feasibility and desirability of breeding livestock for disease resistance. Res. Vet. Sci. 2001, 71, 1–7.
[94]  Kaiko, G.E.; Horvat, J.C.; Beagley, K.W.; Hansbro, P.M. Immunological decision-making: How does the immune system decide to mount a helper T-cell response? Immunology 2008, 123, 326–338.
[95]  Hood, L.; Campbell, J.H.; Elgin, S.C. The organization, expression, and evolution of antibody genes and other multigene families. Annu. Rev. Genet. 1975, 9, 305–353.
[96]  Goldmann, W. PrP genetics in ruminant transmissible spongiform encephalopathies. Vet. Res. 2008, 39, e30, doi:10.1051/vetres:2008010.
[97]  Dickinson, A.; Stamp, J.; Renwick, C.; Smith, W. Genetical Control of Susceptibility to Experimental Challenge with Scrapie in Cheviot Sheep; Report of Scrapie Seminar: Washington, DC, USA, 1964; pp. 249–250.
[98]  Prusiner, S.B. Novel proteinaceous infectious particles cause scrapie. Science 1982, 216, 136–144.
[99]  Carlson, G.A.; Kingsbury, D.T.; Goodman, P.A.; Coleman, S.; Marshall, S.T.; DeArmond, S.; Westaway, D.; Prusiner, S.B. Linkage of prion protein and scrapie incubation time genes. Cell 1986, 46, 503–511, doi:10.1016/0092-8674(86)90875-5.
[100]  Hunter, N.; Hope, J.; McConnell, I.; Dickinson, A.G. Linkage of the scrapie-associated fibril protein (PrP) gene and sinc using congenic mice and restriction fragment length polymorphism analysis. J. Gen. Virol. 1987, 68, 2711–2716, doi:10.1099/0022-1317-68-10-2711.
[101]  Westaway, D.; Goodman, P.A.; Mirenda, C.A.; McKinley, M.P.; Carlson, G.A.; Prusiner, S.B. Distinct prion proteins in short and long scrapie incubation period mice. Cell 1987, 51, 651–662, doi:10.1016/0092-8674(87)90134-6.
[102]  Hunter, N.; Foster, J.D.; Dickinson, A.G.; Hope, J. Linkage of the gene for the scrapie-associated fibril protein (PrP) to the Sip gene in Cheviot sheep. Vet. Rec. 1989, 124, 364–366.
[103]  Bueler, H.; Aguzzi, A.; Sailer, A.; Greiner, R.A.; Autenried, P.; Aguet, M.; Weissmann, C. Mice devoid of PrP are resistant to scrapie. Cell 1993, 73, 1339–1347, doi:10.1016/0092-8674(93)90360-3.
[104]  Prusiner, S.B.; Groth, D.; Serban, A.; Koehler, R.; Foster, D.; Torchia, M.; Burton, D.; Yang, S.L.; DeArmond, S.J. Ablation of the prion protein (PrP) gene in mice prevents scrapie and facilitates production of anti-PrP antibodies. Proc. Natl. Acad. Sci. USA 1993, 90, 10608–10612, doi:10.1073/pnas.90.22.10608.
[105]  Goldmann, W.; Hunter, N.; Foster, J.D.; Salbaum, J.M.; Beyreuther, K.; Hope, J. Two alleles of a neural protein gene linked to scrapie in sheep. Proc. Natl. Acad. Sci. USA 1990, 87, 2476–2480.
[106]  Goldmann, W.; Hunter, N.; Benson, G.; Foster, J.D.; Hope, J. Different scrapie-associated fibril proteins (PrP) are encoded by lines of sheep selected for different alleles of the sip gene. J. Gen. Virol. 1991, 72, 2411–2417, doi:10.1099/0022-1317-72-10-2411.
[107]  Hunter, N.; Foster, J.D.; Benson, G.; Hope, J. Restriction fragment length polymorphisms of the scrapie-associated fibril protein (PrP) gene and their association with susceptibility to natural scrapie in british sheep. J. Gen. Virol. 1991, 72, 1287–1292, doi:10.1099/0022-1317-72-6-1287.
[108]  Hunter, N.; Foster, J.D.; Hope, J. Natural scrapie in British sheep: Breeds, ages and PrP gene polymorphisms. Vet. Rec. 1992, 130, 389–392.
[109]  Hunter, N.; Goldmann, W.; Smith, G.; Hope, J. The association of a codon 136 PrP gene variant with the occurrence of natural scrapie. Arch. Virol. 1994, 137, 171–177.
[110]  Hunter, N.; Goldmann, W.; Foster, J.D.; Cairns, D.; Smith, G. Natural scrapie and PrP genotype: Case-control studies in British sheep. Vet. Rec. 1997, 141, 137–140, doi:10.1136/vr.141.6.137.
[111]  Laplanche, J.L.; Chatelain, J.; Westaway, D.; Thomas, S.; Dussaucy, M.; Brugere-Picoux, J.; Launay, J.M. PrP polymorphisms associated with natural scrapie discovered by denaturing gradient gel electrophoresis. Genomics 1993, 15, 30–37, doi:10.1006/geno.1993.1006.
[112]  Onodera, A.; Ikeda, T.; Horiuchi, M.; Ishiguro, N.; Onuma, M.; Hirano, N.; Mikami, T.; Honda, E.; Hirai, K.; Kai, K.; et al. Survey of natural scrapie in Japan: Analysis of RFLP types of the PrP gene and detection of PrPSc mainly in Suffolk sheep. J. Vet. Med. Sci. 1994, 56, 627–632, doi:10.1292/jvms.56.627.
[113]  Clouscard, C.; Beaudry, P.; Elsen, J.M.; Milan, D.; Dussaucy, M.; Bounneau, C.; Schelcher, F.; Chatelain, J.; Launay, J.M.; Laplanche, J.L. Different allelic effects of the codons 136 and 171 of the prion protein gene in sheep with natural scrapie. J. Gen. Virol. 1995, 76, 2097–2101.
[114]  O'Doherty, E.; Healy, A.; Aherne, M.; Hanrahan, J.P.; Weavers, E.; Doherty, M.; Roche, J.F.; Gunn, M.; Sweeney, T. Prion protein (PrP) gene polymorphisms associated with natural scrapie cases and their flock-mates in Ireland. Res. Vet. Sci. 2002, 73, 243–250.
[115]  Baylis, M.; Chihota, C.; Stevenson, E.; Goldmann, W.; Smith, A.; Sivam, K.; Tongue, S.; Gravenor, M.B. Risk of scrapie in British sheep of different prion protein genotype. J. Gen. Virol. 2004, 85, 2735–2740.
[116]  Baylis, M.; Goldmann, W. The genetics of scrapie in sheep and goats. Curr. Mol. Med. 2004, 4, 385–396, doi:10.2174/1566524043360672.
[117]  Detwiler, L.A.; Baylis, M. The epidemiology of scrapie. Rev. Sci. Tech. 2003, 22, 121–143.
[118]  Ikeda, T.; Horiuchi, M.; Ishiguro, N.; Muramatsu, Y.; Kai-Uwe, G.D.; Shinagawa, M. Amino acid polymorphisms of PrP with reference to onset of scrapie in suffolk and corriedale sheep in Japan. J. Gen. Virol. 1995, 76, 2577–2581, doi:10.1099/0022-1317-76-10-2577.
[119]  Groschup, M.H.; Lacroux, C.; Buschmann, A.; Luhken, G.; Mathey, J.; Eiden, M.; Lugan, S.; Hoffmann, C.; Espinosa, J.C.; Baron, T.; et al. Classic scrapie in sheep with the ARR/ARR prion genotype in Germany and France. Emerg. Infect. Dis. 2007, 13, 1201–1207, doi:10.3201/eid1308.070077.
[120]  Dawson, M.; Hoinville, L.J.; Hosie, B.D.; Hunter, N. Guidance on the use of PrP genotyping as an aid to the control of clinical scrapie. Scrapie information group. Vet. Rec. 1998, 142, 623–625.
[121]  Arnold, M.; Meek, C.; Webb, C.R.; Hoinville, L.J. Assessing the efficacy of a ram-genotyping programme to reduce susceptibility to scrapie in Great Britain. Prev. Vet. Med. 2002, 56, 227–249, doi:10.1016/S0167-5877(02)00159-9.
[122]  Billinis, C.; Psychas, V.; Leontides, L.; Spyrou, V.; Argyroudis, S.; Vlemmas, I.; Leontides, S.; Sklaviadis, T.; Papadopoulos, O. Prion protein gene polymorphisms in healthy and scrapie-affected sheep in Greece. J. Gen. Virol. 2004, 85, 547–554, doi:10.1099/vir.0.19520-0.
[123]  de Vries, F.; Borchers, N.; Hamann, H.; Drogemuller, C.; Reinecke, S.; Lupping, W.; Distl, O. Associations between the prion protein genotype and performance traits of meat breeds of sheep. Vet. Rec. 2004, 155, 140–143, doi:10.1136/vr.155.5.140.
[124]  Alexander, B.M.; Stobart, R.H.; Russell, W.C.; O'Rourke, K.I.; Lewis, G.S.; Logan, J.R.; Duncan, J.V.; Moss, G.E. The incidence of genotypes at codon 171 of the prion protein gene (PRNP) in five breeds of sheep and production traits of ewes associated with those genotypes. J. Anim. Sci. 2005, 83, 455–459.
[125]  Isler, B.J.; Freking, B.A.; Thallman, R.M.; Heaton, M.P.; Leymaster, K.A. Evaluation of associations between prion haplotypes and growth, carcass, and meat quality traits in a Dorset X Romanov sheep population. J. Anim. Sci. 2006, 84, 783–788.
[126]  Vitezica, Z.G.; Moreno, C.R.; Bodin, L.; Francois, D.; Barillet, F.; Brunel, J.C.; Elsen, J.M. No associations between PrP genotypes and reproduction traits in INRA 401 sheep. J. Anim. Sci. 2006, 84, 1317–1322.
[127]  Casellas, J.; Caja, G.; Bach, R.; Francino, O.; Piedrafita, J. Association analyses between the prion protein locus and reproductive and lamb weight traits in Ripollesa sheep. J. Anim. Sci. 2007, 85, 592–597.
[128]  Sweeney, T.; Hanrahan, J.P. The evidence of associations between prion protein genotype and production, reproduction, and health traits in sheep. Vet. Res. 2008, 39, e28.
[129]  Sawalha, R.M.; Brotherstone, S.; Lambe, N.R.; Villanueva, B. Association of the prion protein gene with individual tissue weights in Scottish blackface sheep. J. Anim. Sci. 2008, 86, 1737–1746, doi:10.2527/jas.2007-0650.
[130]  Moore, R.C.; Boulton, K.; Bishop, S.C. Associations of PrP genotype with lamb production traits in three commercial breeds of British lowland sheep. Animal 2009, 3, 1688–1695, doi:10.1017/S175173110999067X.
[131]  Sawalha, R.M.; Villanueva, B.; Brotherstone, S.; Rogers, P.L.; Lewis, R.M. Prediction of prion protein genotype and association of this genotype with lamb performance traits of Suffolk sheep. J. Anim. Sci. 2010, 88, 428–434, doi:10.2527/jas.2009-2009.
[132]  Psifidi, A.; Basdagianni, Z.; Dovas, C.I.; Arsenos, G.; Sinapis, E.; Papanastassopoulou, M.; Banos, G. Characterization of the PRNP gene locus in Chios dairy sheep and its association with milk production and reproduction traits. Anim. Genet. 2011, 42, 406–414, doi:10.1111/j.1365-2052.2010.02159.x.
[133]  Guan, F.; Pan, L.; Li, J.; Tang, H.; Zhu, C.; Shi, G. Polymorphisms of the prion protein gene and their effects on litter size and risk evaluation for scrapie in Chinese Hu sheep. Virus Genes 2011, 43, 147–152, doi:10.1007/s11262-011-0609-5.
[134]  Sawalha, R.M.; Brotherstone, S.; Conington, J.; Villanueva, B. Lambs with scrapie susceptible genotypes have higher postnatal survival. PLoS One 2007, 2, e1236, doi:10.1371/journal.pone.0001236.
[135]  Doeschl-Wilson, A.; Sawalha, R.; Gubbins, S.; Villanueva, B. Implications of conflicting associations of the prion protein (PrP) gene with scrapie susceptibility and fitness on the persistence of scrapie. PLoS One 2009, 4, e7970.
[136]  Gubbins, S.; Cook, C.J.; Hyder, K.; Boulton, K.; Davis, C.; Thomas, E.; Haresign, W.; Bishop, S.C.; Villanueva, B.; Eglin, R.D. Associations between lamb survival and prion protein genotype: Analysis of data for ten sheep breeds in Great Britain. BMC Vet. Res. 2009, 5, e3, doi:10.1186/1746-6148-5-3.
[137]  Zink, M.C.; Narayan, O. Lentivirus-induced interferon inhibits maturation and proliferation of monocytes and restricts the replication of caprine arthritis-encephalitis virus. J. Virol. 1989, 63, 2578–2584.
[138]  Reina, R.; Glaria, I.; Benavides, J.; de Andres, X.; Crespo, H.; Solano, C.; Perez, V.; Lujan, L.; Perez, M.M.; Perez de la Lastra, J.M.; et al. Association of CD80 and CD86 expression levels with disease status of Visna/Maedi virus infected sheep. Viral. Immunol. 2007, 20, 609–622, doi:10.1089/vim.2007.0071.
[139]  Crespo, H.; Reina, R.; Glaria, I.; Ramirez, H.; de Andres, X.; Jauregui, P.; Lujan, L.; Martinez-Pomares, L.; Amorena, B.; de Andres, D.F. Identification of the ovine mannose receptor and its possible role in Visna/Maedi virus infection. Vet. Res. 2011, 42, e28, doi:10.1186/1297-9716-42-28.
[140]  Jauregui, P.; Crespo, H.; Glaria, I.; Lujan, L.; Contreras, A.; Rosati, S.; de Andres, D.; Amorena, B.; Towers, G.J.; Reina, R. Ovine TRIM5alpha can restrict Visna/Maedi virus. J. Virol. 2012, 86, 9504–9509, doi:10.1128/JVI.00440-12.
[141]  Larue, R.S.; Lengyel, J.; Jonsson, S.R.; Andresdottir, V.; Harris, R.S. Lentiviral Vif degrades the APOBEC3Z3/APOBEC3H protein of its mammalian host and is capable of cross-species activity. J. Virol. 2010, 84, 8193–8201, doi:10.1128/JVI.00685-10.
[142]  Cherepanov, P. LEDGF/p75 interacts with divergent lentiviral integrases and modulates their enzymatic activity in vitro. Nucleic Acids Res. 2007, 35, 113–124.
[143]  Mercier, G.; Galien, R.; Emanoil-Ravier, R. Differential effects of ras and jun family members on complex retrovirus promoter activities. Res. Virol. 1994, 145, 361–367, doi:10.1016/S0923-2516(07)80041-0.
[144]  Lena, P.; Freyria, A.M.; Lyon, M.; Cadore, J.L.; Guiguen, F.; Greenland, T.; Belleville, J.; Cordier, G.; Mornex, J.F. Increased expression of tissue factor mRNA and procoagulant activity in ovine lentivirus-infected alveolar macrophages. Res. Virol. 1994, 145, 209–214.
[145]  Shih, D.S.; Carruth, L.M.; Anderson, M.; Clements, J.E. Involvement of FOS and JUN in the activation of visna virus gene expression in macrophages through an AP-1 site in the viral LTR. Virology 1992, 190, 84–91, doi:10.1016/0042-6822(92)91194-Y.
[146]  Morse, B.A.; Carruth, L.M.; Clements, J.E. Targeting of the visna virus tat protein to AP-1 sites: Interactions with the bZIP domains of fos and jun in vitro and in vivo. J. Virol. 1999, 73, 37–45.
[147]  Barber, S.A.; Bruett, L.; Douglass, B.R.; Herbst, D.S.; Zink, M.C.; Clements, J.E. Visna virus-induced activation of MAPK is required for virus replication and correlates with virus-induced neuropathology. J. Virol. 2002, 76, 817–828, doi:10.1128/JVI.76.2.817-828.2002.
[148]  Duval, R.; Bellet, V.; Delebassee, S.; Bosgiraud, C. Implication of caspases during maedi-visna virus-induced apoptosis. J. Gen. Virol. 2002, 83, 3153–3161.
[149]  Zhang, Z.; Harkiss, G.D.; Hopkins, J.; Woodall, C.J. Granulocyte macrophage colony stimulating factor is elevated in alveolar macrophages from sheep naturally infected with maedi-visna virus and stimulates maedi-visna virus replication in macrophages in vitro. Clin. Exp. Immunol. 2002, 129, 240–246, doi:10.1046/j.1365-2249.2002.01826.x.
[150]  Hovden, A.O.; Sommerfelt, M.A. The influence of CD4 and CXCR4 on maedi-visna virus-induced syncytium formation. APMIS 2002, 110, 697–708, doi:10.1034/j.1600-0463.2002.1101003.x.
[151]  Bellet, V.; Delebassee, S.; Bosgiraud, C. Visna/maedi virus-induced apoptosis involves the intrinsic mitochondrial pathway. Arch. Virol. 2004, 149, 1293–1307.
[152]  Bergsteinsdottir, K.; Arnadottir, S.; Torsteinsdottir, S.; Agnarsdottir, G.; Andresdottir, V.; Pettursson, G.; Georgsson, G. Constitutive and visna virus induced expression of class I and II major histocompatibility complex antigens in the central nervous system of sheep and their role in the pathogenesis of visna lesions. Neuropathol. Appl. Neurobiol. 1998, 24, 224–232, doi:10.1046/j.1365-2990.1998.00100.x.
[153]  Legastelois, I.; Levrey, H.; Greenland, T.; Mornex, J.F.; Cordier, G. Visna-maedi virus induces interleukin-8 in sheep alveolar macrophages through a tyrosine-kinase signaling pathway. Am. J. Respir. Cell Mol. Biol. 1998, 18, 532–537, doi:10.1165/ajrcmb.18.4.2812.
[154]  Moreno, B.; Woodall, C.J.; Watt, N.J.; Harkiss, G.D. Transforming growth factor-beta 1 (TGF-beta1) expression in ovine lentivirus-induced lymphoid interstitial pneumonia. Clin. Exp. Immunol. 1998, 112, 74–83, doi:10.1046/j.1365-2249.1998.00553.x.
[155]  Woodall, C.J.; Maclaren, L.J.; Watt, N.J. Differential levels of mRNAs for cytokines, the interleukin-2 receptor and class II DR/DQ genes in ovine interstitial pneumonia induced by maedi visna virus infection. Vet. Pathol. 1997, 34, 204–211.
[156]  Sharmila, C.; Williams, J.W.; Reddy, P.G. Effect of caprine arthritis-encephalitis virus infection on expression of interleukin-16 in goats. Am. J. Vet. Res. 2002, 63, 1418–1422, doi:10.2460/ajvr.2002.63.1418.
[157]  Adeyemo, O.; Gao, R.J.; Lan, H.C. Cytokine production in vitro by macrophages of goats with caprine arthritis-encephalitis. Cell Mol. Biol. (Noisy-le-grand) 1997, 43, 1031–1037.
[158]  Lechner, F.; Vogt, H.R.; Seow, H.F.; von Bodungen, U.; Bertoni, G.; Zurbriggen, A.; Peterhans, E. Expression of TNF alpha in arthritis caused by caprine arthritis encephalitis virus. Vet. Immunol. Immunopathol. 1996, 54, 281–289, doi:10.1016/S0165-2427(96)05701-7.
[159]  Lechner, F.; Machado, J.; Bertoni, G.; Seow, H.F.; Dobbelaere, D.A.; Peterhans, E. Caprine arthritis encephalitis virus dysregulates the expression of cytokines in macrophages. J. Virol. 1997, 71, 7488–7497.
[160]  Lechner, F.; Schutte, A.; von Bodungen, U.; Bertoni, G.; Pfister, H.; Jungi, T.W.; Peterhans, E. Inducible nitric oxide synthase is expressed in joints of goats in the late stage of infection with caprine arthritis encephalitis virus. Clin. Exp. Immunol. 1999, 117, 70–75, doi:10.1046/j.1365-2249.1999.00932.x.
[161]  Sepp, T.; Tong-Starksen, S.E. STAT1 pathway is involved in activation of caprine arthritis-encephalitis virus long terminal repeat in monocytes. J. Virol. 1997, 71, 771–777.
[162]  Tong-Starksen, S.E.; Sepp, T.; Pagtakhan, A.S. Activation of caprine arthritis-encephalitis virus long terminal repeat by gamma interferon. J. Virol. 1996, 70, 595–599.
[163]  Heaton, M.P.; Kalbfleisch, T.S.; Petrik, D.T.; Simpson, B.; Kijas, J.W.; Clawson, M.L.; Chitko-McKown, C.G.; Harhay, G.P.; Leymaster, K.A. Genetic testing for tmem154 mutations associated with lentivirus susceptibility in sheep. PLoS One 2013, 8, e55490.
[164]  Vassy, J.L.; Meigs, J.B. Is genetic testing useful to predict type 2 diabetes? Best Pract. Res. Clin. Endocrinol. Metab. 2012, 26, 189–201, doi:10.1016/j.beem.2011.09.002.
[165]  Yasuda, K.; Miyake, K.; Horikawa, Y.; Hara, K.; Osawa, H.; Furuta, H.; Hirota, Y.; Mori, H.; Jonsson, A.; Sato, Y.; et al. Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus. Nat. Genet. 2008, 40, 1092–1097.
[166]  Grant, S.F.; Thorleifsson, G.; Reynisdottir, I.; Benediktsson, R.; Manolescu, A.; Sainz, J.; Helgason, A.; Stefansson, H.; Emilsson, V.; Helgadottir, A.; et al. Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat. Genet. 2006, 38, 320–323.
[167]  Helgason, A.; Palsson, S.; Thorleifsson, G.; Grant, S.F.; Emilsson, V.; Gunnarsdottir, S.; Adeyemo, A.; Chen, Y.; Chen, G.; Reynisdottir, I.; et al. Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution. Nat. Genet. 2007, 39, 218–225.
[168]  Zeggini, E.; Scott, L.J.; Saxena, R.; Voight, B.F.; Marchini, J.L.; Hu, T.; de Bakker, P.I.; Abecasis, G.R.; Almgren, P.; Andersen, G.; et al. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat. Genet. 2008, 40, 638–645.
[169]  Baack, E.J.; Rieseberg, L.H. A genomic view of introgression and hybrid speciation. Curr. Opin. Genet. Dev. 2007, 17, 513–518, doi:10.1016/j.gde.2007.09.001.
[170]  Gootwine, E. Mini review: Breeding Awassi and Assaf sheep for diverse management conditions. Trop. Anim. Health Prod. 2011, 43, 1289–1296, doi:10.1007/s11250-011-9852-y.
[171]  Hu, Z.L.; Fritz, E.R.; Reecy, J.M. AnimalQTLdb: A livestock QTL database tool set for positional QTL information mining and beyond. Nucleic Acids Res. 2007, 35, D604–D609, doi:10.1093/nar/gkl946.
[172]  Hu, Z.L.; Reecy, J.M. Animal QTLdb: Beyond a repository. A public platform for QTL comparisons and integration with diverse types of structural genomic information. Mamm. Genome 2007, 18, 1–4, doi:10.1007/s00335-006-0105-8.
[173]  Lim, J.K.; Glass, W.G.; McDermott, D.H.; Murphy, P.M. Ccr5: No longer a “good for nothing” gene—Chemokine control of west Nile virus infection. Trends Immunol. 2006, 27, 308–312, doi:10.1016/
[174]  Lim, J.K.; Louie, C.Y.; Glaser, C.; Jean, C.; Johnson, B.; Johnson, H.; McDermott, D.H.; Murphy, P.M. Genetic deficiency of chemokine receptor CCR5 is a strong risk factor for symptomatic West Nile virus infection: A meta-analysis of 4 cohorts in the US epidemic. J. Infect. Dis. 2008, 197, 262–265.
[175]  Dean, M.; Carrington, M.; Winkler, C.; Huttley, G.A.; Smith, M.W.; Allikmets, R.; Goedert, J.J.; Buchbinder, S.P.; Vittinghoff, E.; Gomperts, E.; et al. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Science 1996, 273, 1856–1862, doi:10.1126/science.273.5283.1856.
[176]  Liu, R.; Paxton, W.A.; Choe, S.; Ceradini, D.; Martin, S.R.; Horuk, R.; MacDonald, M.E.; Stuhlmann, H.; Koup, R.A.; Landau, N.R. Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell 1996, 86, 367–377, doi:10.1016/S0092-8674(00)80110-5.
[177]  Samson, M.; Libert, F.; Doranz, B.J.; Rucker, J.; Liesnard, C.; Farber, C.M.; Saragosti, S.; Lapoumeroulie, C.; Cognaux, J.; Forceille, C.; et al. Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature 1996, 382, 722–725, doi:10.1038/382722a0.
[178]  Serrano, C.; Hammouchi, M.; Benomar, A.; Lyahyai, J.; Ranera, B.; Acin, C.; El Hamidi, M.; Monzon, M.; Badiola, J.J.; Tligui, N.; et al. PRNP haplotype distribution in Moroccan goats. Anim. Genet. 2009, 40, 565–568, doi:10.1111/j.1365-2052.2009.01873.x.
[179]  Lan, Z.; Wang, Z.L.; Liu, Y.; Zhang, X. Prion protein gene (PRNP) polymorphisms in Xinjiang local sheep breeds in China. Arch. Virol. 2006, 151, 2095–2101.
[180]  Acin, C.; Martin-Burriel, I.; Goldmann, W.; Lyahyai, J.; Monzon, M.; Bolea, R.; Smith, A.; Rodellar, C.; Badiola, J.J.; Zaragoza, P. Prion protein gene polymorphisms in healthy and scrapie-affected Spanish sheep. J. Gen. Virol. 2004, 85, 2103–2110.
[181]  Billinis, C.; Panagiotidis, C.H.; Psychas, V.; Argyroudis, S.; Nicolaou, A.; Leontides, S.; Papadopoulos, O.; Sklaviadis, T. Prion protein gene polymorphisms in natural goat scrapie. J. Gen. Virol. 2002, 83, 713–721.
[182]  Hotzel, I.; Cheevers, W.P. A maedi-visna virus strain K1514 receptor gene is located in sheep chromosome 3p and the syntenic region of human chromosome 2. J. Gen. Virol. 2002, 83, 1759–1764.
[183]  Lyall, J.W.; Solanky, N.; Tiley, L.S. Restricted species tropism of maedi-visna virus strain EV-1 is not due to limited receptor distribution. J. Gen. Virol. 2000, 81, 2919–2927.
[184]  Waterston, R.H.; Lindblad-Toh, K.; Birney, E.; Rogers, J.; Abril, J.F.; Agarwal, P.; Agarwala, R.; Ainscough, R.; Alexandersson, M.; An, P.; et al. Initial sequencing and comparative analysis of the mouse genome. Nature 2002, 420, 520–562, doi:10.1038/nature01262.
[185]  Hotzel, I.; Cheevers, W. Differential receptor usage of small ruminant lentiviruses in ovine and caprine cells: Host range but not cytopathic phenotype is determined by receptor usage. Virology 2002, 301, 21–31.
[186]  Skraban, R.; Matthiasdottir, S.; Torsteinsdottir, S.; Agnarsdottir, G.; Gudmundsson, B.; Georgsson, G.; Meloen, R.H.; Andresson, O.S.; Staskus, K.A.; Thormar, H.; et al. Naturally occurring mutations within 39 amino acids in the envelope glycoprotein of maedi-visna virus alter the neutralization phenotype. J. Virol. 1999, 73, 8064–8072.
[187]  Murphy, B.; McElliott, V.; Vapniarsky, N.; Oliver, A.; Rowe, J. Tissue tropism and promoter sequence variation in caprine arthritis encephalitis virus infected goats. Virus Res. 2010, 151, 177–184, doi:10.1016/j.virusres.2010.05.002.
[188]  Valas, S.; Rolland, M.; Perrin, C.; Perrin, G.; Mamoun, R.Z. Characterization of a new 5' splice site within the caprine arthritis encephalitis virus genome: Evidence for a novel auxiliary protein. Retrovirology 2008, 5, e22.
[189]  Hotzel, I.; Cheevers, W.P. Mutations increasing exposure of a receptor binding site epitope in the soluble and oligomeric forms of the caprine arthritis-encephalitis lentivirus envelope glycoprotein. Virology 2005, 339, 261–272, doi:10.1016/j.virol.2005.05.028.
[190]  Angelopoulou, K.; Brellou, G.D.; Greenland, T.; Vlemmas, I. A novel deletion in the LTR region of a Greek small ruminant lentivirus may be associated with low pathogenicity. Virus Res. 2006, 118, 178–184, doi:10.1016/j.virusres.2005.12.010.
[191]  Angelopoulou, K.; Poutahidis, T.; Brellou, G.D.; Greenland, T.; Vlemmas, I. A deletion in the R region of long terminal repeats in small ruminant lentiviruses is associated with decreased pathology in the lung. Vet. J. 2008, 175, 346–355, doi:10.1016/j.tvjl.2007.01.025.
[192]  Oskarsson, T.; Hreggvidsdottir, H.S.; Agnarsdottir, G.; Matthiasdottir, S.; Ogmundsdottir, M.H.; Jonsson, S.R.; Georgsson, G.; Ingvarsson, S.; Andresson, O.S.; Andresdottir, V. Duplicated sequence motif in the long terminal repeat of maedi-visna virus extends cell tropism and is associated with neurovirulence. J. Virol. 2007, 81, 4052–4057, doi:10.1128/JVI.02319-06.
[193]  Barros, S.C.; Ramos, F.; Duarte, M.; Fagulha, T.; Cruz, B.; Fevereiro, M. Genomic characterization of a slow/low maedi visna virus. Virus Genes 2004, 29, 199–210, doi:10.1023/B:VIRU.0000036380.01957.37.
[194]  Cardinaux, L.; Zahno, M.L.; Deubelbeiss, M.; Zanoni, R.; Vogt, H.R.; Bertoni, G. Virological and phylogenetic characterization of attenuated small ruminant lentivirus isolates eluding efficient serological detection. Vet. Microbiol. 2013, 162, 572–581, doi:10.1016/j.vetmic.2012.11.017.
[195]  Zanoni, R.G. Phylogenetic analysis of small ruminant lentiviruses. J. Gen. Virol. 1998, 79, 1951–1961.
[196]  Shah, C.; Boni, J.; Huder, J.B.; Vogt, H.R.; Muhlherr, J.; Zanoni, R.; Miserez, R.; Lutz, H.; Schupbach, J. Phylogenetic analysis and reclassification of caprine and ovine lentiviruses based on 104 new isolates: Evidence for regular sheep-to-goat transmission and worldwide propagation through livestock trade. Virology 2004, 319, 12–26, doi:10.1016/j.virol.2003.09.047.
[197]  Gudmundsson, B.; Jonsson, S.R.; Olafsson, O.; Agnarsdottir, G.; Matthiasdottir, S.; Georgsson, G.; Torsteinsdottir, S.; Svansson, V.; Kristbjornsdottir, H.B.; Franzdottir, S.R.; et al. Simultaneous mutations in CA and Vif of Maedi-Visna virus cause attenuated replication in macrophages and reduced infectivity in vivo. J. Virol. 2005, 79, 15038–15042, doi:10.1128/JVI.79.24.15038-15042.2005.
[198]  Murphy, B.; Hillman, C.; Castillo, D.; Vapniarsky, N.; Rowe, J. The presence or absence of the gamma-activated site determines IFN gamma-mediated transcriptional activation in CAEV promoters cloned from the mammary gland and joint synovium of a single CAEV-infected goat. Virus Res. 2012, 163, 537–545, doi:10.1016/j.virusres.2011.12.001.
[199]  Gomez-Lucia, E.; Rowe, J.; Collar, C.; Murphy, B. Diversity of caprine arthritis-encephalitis virus promoters isolated from goat milk and passaged in vitro. Vet. J. 2013. in press. Available online: (accessed on 13 June 2013).
[200]  Hess, J.L.; Pyper, J.M.; Clements, J.E. Nucleotide sequence and transcriptional activity of the caprine arthritis-encephalitis virus long terminal repeat. J. Virol. 1986, 60, 385–393.
[201]  Hess, J.L.; Small, J.A.; Clements, J.E. Sequences in the visna virus long terminal repeat that control transcriptional activity and respond to viral trans-activation: Involvement of AP-1 sites in basal activity and trans-activation. J. Virol. 1989, 63, 3001–3015.
[202]  Gabuzda, D.H.; Hess, J.L.; Small, J.A.; Clements, J.E. Regulation of the visna virus long terminal repeat in macrophages involves cellular factors that bind sequences containing AP-1 sites. Mol. Cell. Biol. 1989, 9, 2728–2733.
[203]  Small, J.A.; Bieberich, C.; Ghotbi, Z.; Hess, J.; Scangos, G.A.; Clements, J.E. The visna virus long terminal repeat directs expression of a reporter gene in activated macrophages, lymphocytes, and the central nervous systems of transgenic mice. J. Virol. 1989, 63, 1891–1896.
[204]  Barros, S.C.; Andresdottir, V.; Fevereiro, M. Cellular specificity and replication rate of Maedi Visna virus in vitro can be controlled by LTR sequences. Arch. Virol. 2005, 150, 201–213, doi:10.1007/s00705-004-0436-2.
[205]  Maillard, J.C.; Berthier, D.; Chantal, I.; Thevenon, S.; Sidibe, I.; Stachurski, F.; Belemsaga, D.; Razafindraibe, H.; Elsen, J.M. Selection assisted by a BoLA-DR/DQ haplotype against susceptibility to bovine dermatophilosis. Genet. Sel. Evol. 2003, 35, S193–S200, doi:10.1186/1297-9686-35-S1-S193.
[206]  Bertoni, G.; Blacklaws, B. Small ruminant lentiviruses and cross-species transmission. In Lentiviruses and Macrophages: Molecular and Cellular Interactions; Caister Academic Press: Norfolk, UK, 2010; p. 277.
[207]  Duggal, N.K.; Emerman, M. Evolutionary conflicts between viruses and restriction factors shape immunity. Nat. Rev. Immunol. 2012, 12, 687–695, doi:10.1038/nri3295.
[208]  Singh, R.P.; Huerta-Espino, J.; William, H.M. Genetics and breeding for durable resistance to leaf and stripe rusts in wheat. Turk. J. Agric. For. 2005, 29, 121–127.
[209]  Mani, R.; St Onge, R.P.; Hartman, J.L.T.; Giaever, G.; Roth, F.P. Defining genetic interaction. Proc. Natl. Acad. Sci. USA 2008, 105, 3461–3466.
[210]  Alper, C.A.; Awdeh, Z.; Yunis, E.J. Conserved, extended MHC haplotypes. Exp. Clin. Immunogenet. 1992, 9, 58–71.
[211]  Trowsdale, J. HLA genomics in the third millennium. Curr. Opin. Immunol. 2005, 17, 498–504.
[212]  McNeilly, T.N.; Tennant, P.; Lujan, L.; Perez, M.; Harkiss, G.D. Differential infection efficiencies of peripheral lung and tracheal tissues in sheep infected with visna/maedi virus via the respiratory tract. J. Gen. Virol. 2007, 88, 670–679, doi:10.1099/vir.0.82434-0.
[213]  McNeilly, T.N.; Baker, A.; Brown, J.K.; Collie, D.; Maclachlan, G.; Rhind, S.M.; Harkiss, G.D. Role of alveolar macrophages in respiratory transmission of visna/maedi virus. J. Virol. 2008, 82, 1526–1536.
[214]  Singh, D.K.; Chebloune, Y.; Mselli-Lakhal, L.; Karr, B.M.; Narayan, O. Ovine lentivirus-infected macrophages mediate productive infection in cell types that are not susceptible to infection with cell-free virus. J. Gen. Virol. 1999, 80, 1437–1444.
[215]  Villoria, M.; Leginagoikoa, I.; Luján, L.; Pérez, M.; Salazar, E.; Berriatua, E.; Juste, R.; Minguijón, E. Detection of small ruminant lentivirus in environmental samples of air and water. Small Rumin. Res. 2013, 110, 155–160, doi:10.1016/j.smallrumres.2012.11.025.
[216]  Kijas, J.W.; Ortiz, J.S.; McCulloch, R.; James, A.; Brice, B.; Swain, B.; Tosser-Klopp, G. Genetic diversity and investigation of polledness in divergent goat populations using 52 088 SNPs. Anim. Genet. 2013, 44, 325–335, doi:10.1111/age.12011.
[217]  Hayes, B.J.; Lewin, H.A.; Goddard, M.E. The future of livestock breeding: Genomic selection for efficiency, reduced emissions intensity, and adaptation. Trends. Genet. 2013, 29, 206–214, doi:10.1016/j.tig.2012.11.009.
[218]  Kijas, J.W.; Lenstra, J.A.; Hayes, B.; Boitard, S.; Porto Neto, L.R.; San Cristobal, M.; Servin, B.; McCulloch, R.; Whan, V.; Gietzen, K.; et al. Genome-wide analysis of the world’s sheep breeds reveals high levels of historic mixture and strong recent selection. PLoS Biol. 2012, 10, e1001258, doi:10.1371/journal.pbio.1001258.
[219]  Berry, D.P.; Bermingham, M.L.; Good, M.; More, S.J. Genetics of animal health and disease in cattle. Ir. Vet. J. 2011, 64, e5, doi:10.1186/2046-0481-64-5.
[220]  Daetwyler, H.; Hickey, J.; Henshall, J.; Dominik, S.; Gredler, B.; van der Werf, J.; Hayes, B. Accuracy of estimated genomic breeding values for wool and meat traits in a multi-breed sheep population. Anim. Prod. Sci. 2010, 50, 1004–1010, doi:10.1071/AN10096.
[221]  Duchemin, S.; Colombani, C.; Legarra, A.; Baloche, G.; Larroque, H.; Astruc, J.-M.; Barillet, F.; Robert-Granié, C.; Manfredi, E. Genomic selection in the French Lacaune dairy sheep breed. J. Dairy Sci. 2012, 95, 2723–2733, doi:10.3168/jds.2011-4980.
[222]  Daetwyler, H.D.; Swan, A.A.; van Der Werf, J.H.; Hayes, B.J. Accuracy of pedigree and genomic predictions of carcass and novel meat quality traits in multi-breed sheep data assessed by cross-validation. Genet. Sel. Evol. 2012, 44, e33, doi:10.1186/1297-9686-44-33.
[223]  Daetwyler, H.; Kemper, K.; van der Werf, J.; Hayes, B. Components of the accuracy of genomic prediction in a multi-breed sheep population. J. Anim. Sci. 2012, 90, 3375–3384.
[224]  Erbe, M.; Hayes, B.; Matukumalli, L.; Goswami, S.; Bowman, P.; Reich, C.; Mason, B.; Goddard, M. Improving accuracy of genomic predictions within and between dairy cattle breeds with imputed high-density single nucleotide polymorphism panels. J. Dairy Sci. 2012, 95, 4114–4129, doi:10.3168/jds.2011-5019.


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