Immune responses against classical swine fever virus: Between ignorance and lunacy

Frontiers in Veterinary Science

Volumn 2, Issue MAY, 2015, Pages

  Summerfield, Artur ^a   Ruggli, Nicolas ^a  

^a INSTITUTE OF VIROLOGY AND IMMUNOLOGY   (Switzerland)

Author keywords

Classical swine fever; Dendritic cells; Interferon; Macrophages; Virulence

Indexed keywords

EID: 84971242086     PISSN: None     EISSN: 22971769     Source Type: Journal    
DOI: 10.3389/fvets.2015.00010     Document Type: Review

References (107)

1. Thiel H-J, Plagemann PGW, Moennig V. Pestiviruses. In: Fields BN, Knipe DM, Howley PM, editors. Fields Virology. Philadelphia, PA: Lippincott-Raven Publishers (1996). p. 1059-73
2. Ressang AA. Studies on the pathogenesis of hog cholera. II. Virus distribution in tissue and the morphology of the immune response. Zentralbl Veterinarmed B (1973) 20:272-88. doi:10.1111/j.1439-0450.1973.tb01127.x
3. Trautwein G, Leiss B. Pathology and Pathogenesis of the Disease, Classical Swine Fever and Related Infections. Boston, MA: Martinus Nijhoff Publishing (1988). p. 27-54
4. Gomez-Villamandos JC, Ruiz-Villamor E, Bautista MJ, Sanchez CP, Sanchez-Cordon PJ, Salguero FJ, et al. Morphological and immunohistochemical changes in splenic macrophages of pigs infected with classical swine fever. J Comp Pathol (2001) 125:98-109. doi:10.1053/jcpa.2001.0487
5. Sanchez-Cordon PJ, Romanini S, Salguero FJ, Nunez A, Bautista MJ, Jover A, et al. Apoptosis of thymocytes related to cytokine expression in experimental classical swine fever. J Comp Pathol (2002) 127:239-48. doi:10.1053/jcpa.2002.0587
6. Susa M, Konig M, Saalmuller A, Reddehase MJ, Thiel HJ. Pathogenesis of classical swine fever: B-lymphocyte deficiency caused by hog cholera virus. J Virol (1992) 66:1171-5
7. Summerfield A, Hofmann MA, McCullough KC. Low density blood granulocytic cells induced during classical swine fever are targets for virus infection. Vet Immunol Immunopathol (1998) 63:289-301. doi:10.1016/S0165-2427(98)00108-1
8. Knoetig SM, Summerfield A, Spagnuolo-Weaver M, McCullough KC. Immunopathogenesis of classical swine fever: role of monocytic cells. Immunology (1999) 97:359-66. doi:10.1046/j.1365-2567.1999.00775.x
9. Carrasco CP, Rigden RC, Schaffner R, Gerber H, Neuhaus V, Inumaru S, et al. Porcine dendritic cells generated in vitro: morphological, phenotypic and functional properties. Immunology (2001) 104:175-84. doi:10.1046/j.1365-2567.2001.01299.x
10. Jamin A, Gorin S, Cariolet R, Le Potier MF, Kuntz-Simon G. Classical swine fever virus induces activation of plasmacytoid and conventional dendritic cells in tonsil, blood, and spleen of infected pigs. Vet Res (2008) 39:7. doi:10.1051/vetres:2007045
11. Summerfield A, Knoetig SM, Tschudin R, McCullough KC. Pathogenesis of granulocytopenia and bone marrow atrophy during classical swine fever involves apoptosis and necrosis of uninfected cells. Virology (2000) 272:50-60. doi:10.1006/viro.2000.0361
12. Liu J, Fan XZ, Wang Q, Xu L, Zhao QZ, Huang W, et al. Dynamic distribution and tissue tropism of classical swine fever virus in experimentally infected pigs. Virol J (2011) 8:201. doi:10.1186/1743-422X-8-201
13. Pauly T, Konig M, Thiel HJ, Saalmuller A. Infection with classical swine fever virus: effects on phenotype and immune responsiveness of porcine T lymphocytes. J Gen Virol (1998) 79(Pt 1):31-40
14. Kaden V, Lange E, Faust A, Teifke JP. Value of skin punch biopsies for the diagnosis of acute classical swine fever. J Vet Diagn Invest (2007) 19:697-701. doi:10.1177/104063870701900614
15. Summerfield A, Knotig SM, McCullough KC. Lymphocyte apoptosis during classical swine fever: implication of activation-induced cell death. J Virol (1998) 72:1853-61
16. Bautista MJ, RuizVillamor E, Salguero FJ, SanchezCordon PJ, Carrasco L, GomezVillamandos JC. Early platelet aggregation as a cause of thrombocytopenia in classical swine fever 1842. Vet Pathol (2002) 39:84-91. doi:10.1354/vp.39-1-84
17. Gomez-Villamandos JC, Salguero FJ, Ruiz-Villamor E, Sanchez-Cordon PJ, Bautista MJ, Sierra MA. Classical swine fever: pathology of bone marrow. Vet Pathol (2003) 40:157-63. doi:10.1354/vp.40-2-157
18. Sanchez-Cordon PJ, Romanini S, Salguero FJ, Ruiz-Villamor E, Carrasco L, Gomez-Villamandos JC. A histopathologic, immunohistochemical, and ultrastructural study of the intestine in pigs inoculated with classical swine fever virus. Vet Pathol (2003) 40:254-62. doi:10.1354/vp.40-3-254
19. Blome S, Meindl-Bohmer A, Nowak G, Moennig V. Disseminated intravascular coagulation does not play a major role in the pathogenesis of classical swine fever. Vet Microbiol (2013) 162:360-8. doi:10.1016/j.vetmic.2012.10.008
20. Ruggli N, Summerfield A, Fiebach AR, Guzylack-Piriou L, Bauhofer O, Lamm CG, et al. Classical swine fever virus can remain virulent after specific elimination of the interferon regulatory factor 3-degrading function of Npro. J Virol (2009) 83:817-29. doi:10.1128/JVI.01509-08
21. Summerfield A, Alves M, Ruggli N, de Bruin MG, McCullough KC. High IFN-alpha responses associated with depletion of lymphocytes and natural IFN-producing cells during classical swine fever. J Interferon Cytokine Res (2006) 26:248-55. doi:10.1089/jir.2006.26.248
22. von Rosen T, Lohse L, Nielsen J, Uttenthal A. Classical swine fever virus infection modulates serum levels of INF-alpha, IL-8 and TNF-alpha in 6-month-old pigs. Res Vet Sci (2013) 95:1262-7. doi:10.1016/j.rvsc.2013.09.011
23. Renson P, Blanchard Y, Le Dimna M, Felix H, Cariolet R, Jestin A, et al. Acute induction of cell death-related IFN stimulated genes (ISG) differentiates highly from moderately virulent CSFV strains. Vet Res (2010) 41:7. doi:10.1051/vetres/2009055
24. Summerfield A. Viewpoint: factors involved in type I interferon responses during porcine virus infections. Vet Immunol Immunopathol (2012) 148:168-71. doi:10.1016/j.vetimm.2011.03.011
25. Sanchez-Cordon PJ, Nunez A, Salguero FJ, Pedrera M, Fernandez de MM, Gomez-Villamandos JC. Lymphocyte apoptosis and thrombocytopenia in spleen during classical swine fever: role of macrophages and cytokines. Vet Pathol (2005) 42:477-88. doi:10.1354/vp.42-4-477
26. Gomez-Villamandos JC, Ruiz-Villamor E, Bautista MJ, Quezada M, Sanchez CP, Salguero FJ, et al. Pathogenesis of classical swine fever: renal haemorrhages and erythrodiapedesis. J Comp Pathol (2000) 123:47-54. doi:10.1053/jcpa.2000.0385
27. Carrasco L, Ruiz-Villamor E, Gomez-Villamandos JC, Salguero FJ, Bautista MJ, Macia M, et al. Classical swine fever: morphological and morphometrical study of pulmonary intravascular macrophages. J Comp Pathol (2001) 125:1-7. doi:10.1053/jcpa.2001.0470
28. Nunez A, Gomez-Villamandos JC, Sanchez-Cordon PJ, Fernandez de Marco M, Pedrera M, Salguero FJ, et al. Expression of proinflammatory cytokines by hepatic macrophages in acute classical swine fever. J Comp Pathol (2005) 133:23-32. doi:10.1016/j.jcpa.2005.01.003
29. Summerfield A, Auray G, Ricklin M. Comparative dendritic cell biology of veterinary mammals. Annu Rev Anim Biosci (2014) 3:533-57. doi:10.1146/annurev-animal-022114-111009
30. Merad M, Sathe P, Helft J, Miller J, Mortha A. The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu Rev Immunol (2013) 31:563-604. doi:10.1146/annurev-immunol-020711-074950
31. Suradhat S, Sada W, Buranapraditkun S, Damrongwatanapokin S. The kinetics of cytokine production and CD25 expression by porcine lymphocyte subpopulations following exposure to classical swine fever virus (CSFV). Vet Immunol Immunopathol (2005) 106:197-208. doi:10.1016/j.vetimm.2005.02.017
32. Suradhat S, Intrakamhaeng M, Damrongwatanapokin S. The correlation of virus-specific interferon-gamma production and protection against classical swine fever virus infection. Vet Immunol Immunopathol (2001) 83:177-89. doi:10.1016/S0165-2427(01)00389-0
33. Sanchez-Cordon PJ, Nunez A, Salguero FJ, Carrasco L, Gomez-Villamandos JC. Evolution of T lymphocytes and cytokine expression in classical swine fever (CSF) virus infection. J Comp Pathol (2005) 132:249-60. doi:10.1016/j.jcpa.2004.10.002
34. Sanchez-Cordon PJ, Romero-Trevejo JL, Pedrera M, Raya AI, Gomez-Villamandos JC. The role of B cells in the immune response to pestivirus (classical swine fever virus). J Comp Pathol (2006) 135:32-41. doi:10.1016/j.jcpa.2006.04.001
35. Tarradas J, de la Torre ME, Rosell R, Perez LJ, Pujols J, Munoz M, et al. The impact of CSFV on the immune response to control infection. Virus Res (2014) 185:82-91. doi:10.1016/j.virusres.2014.03.004
36. Nielsen J, Lohse L, Rasmussen TB, Uttenthal A. Classical swine fever in 6-and 11-week-old pigs: haematological and immunological parameters are modulated in pigs with mild clinical disease. Vet Immunol Immunopathol (2010) 138:159-73. doi:10.1016/j.vetimm.2010.07.012
37. Summerfield A, McNeilly F, Walker I, Allan G, Knoetig SM, McCullough KC. Depletion of CD4(+) and CD8(high+) T-cells before the onset of viraemia during classical swine fever. Vet Immunol Immunopathol (2001) 78:3-19. doi:10.1016/S0165-2427(00)00248-8
38. Depner KR, Hinrichs U, Bickhardt K, Greiser-Wilke I, Pohlenz J, Moennig V, et al. Influence of breed-related factors on the course of classical swine fever virus infection. Vet Rec (1997) 140:506-7. doi:10.1136/vr.140.19.506
39. Moennig V, Floegel-Niesmann G, Greiser-Wilke I. Clinical signs and epidemiology of classical swine fever: a review of new knowledge. Vet J (2003) 165:11-20. doi:10.1016/S1090-0233(02)00112-0
40. Van Oirschot JT, Liess B. Description of the Virus Infection, Classical Swine Fever and Related Viral Infections. Boston, MA: Martinus Nijhoff Publishing (1988). p. 1-18
41. Weesendorp E, Backer J, Stegeman A, Loeffen W. Transmission of classical swine fever virus depends on the clinical course of infection which is associated with high and low levels of virus excretion. Vet Microbiol (2011) 147:262-73. doi:10.1016/j.vetmic.2010.06.032
42. Weesendorp E, Stegeman A, Loeffen W. Dynamics of virus excretion via different routes in pigs experimentally infected with classical swine fever virus strains of high, moderate or low virulence. Vet Microbiol (2009) 133:9-22. doi:10.1016/j.vetmic.2008.06.008
43. Korn G, Lorenz RJ. [Blood-pictures in different courses of swine fever infection concerning lymphocytic reactions, cellnecrobiosis, moving forms of lymphocytes ("lysocytes") and reactions of the bone-marrow (author's transl)]. Zentralbl Bakteriol Orig A (1974) 229:299-322
44. Narita M, Kawashima K, Shimizu M. Viral antigen and B and T lymphocytes in lymphoid tissues of gnotobiotic piglets infected with hog cholera virus. J Comp Pathol (1996) 114:257-63. doi:10.1016/S0021-9975(96)80047-8
45. Szymanski MR, Fiebach AR, Tratschin JD, Gut M, Ramanujam VM, Gottipati K, et al. Zinc binding in pestivirus N(pro) is required for interferon regulatory factor 3 interaction and degradation. J Mol Biol (2009) 391:438-49. doi:10.1016/j.jmb.2009.06.040
46. Gottipati K, Ruggli N, Gerber M, Tratschin JD, Benning M, Bellamy H, et al. The structure of classical swine fever virus N(pro): a novel cysteine autoprotease and zinc-binding protein involved in subversion of type I interferon induction. PLoS Pathog (2013) 9:e1003704. doi:10.1371/journal.ppat.1003704
47. Bauhofer O, Summerfield A, Sakoda Y, Tratschin JD, Hofmann MA, Ruggli N. Classical swine fever virus Npro interacts with interferon regulatory factor 3 and induces its proteasomal degradation. J Virol (2007) 81:3087-96. doi:10.1128/JVI.02032-06
48. Ruggli N, Bird BH, Liu L, Bauhofer O, Tratschin JD, Hofmann MA. N(pro) of classical swine fever virus is an antagonist of double-stranded RNA-mediated apoptosis and IFN-alpha/beta induction. Virology (2005) 340(2):265-76. doi:10.1016/j.virol.2005.06.033
49. Seago J, Hilton L, Reid E, Doceul V, Jeyatheesan J, Moganeradj K, et al. The Npro product of classical swine fever virus and bovine viral diarrhea virus uses a conserved mechanism to target interferon regulatory factor-3. J Gen Virol (2007) 88:3002-6. doi:10.1099/vir.0.82934-0
50. Chen Z, Rijnbrand R, Jangra RK, Devaraj SG, Qu L, Ma Y, et al. Ubiquitination and proteasomal degradation of interferon regulatory factor-3 induced by Npro from a cytopathic bovine viral diarrhea virus. Virology (2007) 366:277-92. doi:10.1016/j.virol.2007.04.023
51. Hilton L, Moganeradj K, Zhang G, Chen YH, Randall RE, McCauley JW, et al. The NPro product of bovine viral diarrhea virus inhibits DNA binding by interferon regulatory factor 3 and targets it for proteasomal degradation. J Virol (2006) 80:11723-32. doi:10.1128/JVI.01145-06
52. Honda K, Yanai H, Negishi H, Asagiri M, Sato M, Mizutani T, et al. IRF-7 is the master regulator of type-I interferon-dependent immune responses. Nature (2005) 434:772-7. doi:10.1038/nature03464
53. Fiebach AR, Guzylack-Piriou L, Python S, Summerfield A, Ruggli N. Classical swine fever virus N(pro) limits type I interferon induction in plasmacytoid dendritic cells by interacting with interferon regulatory factor 7. J Virol (2011) 85:8002-11. doi:10.1128/JVI.00330-11
54. Husser L, Ruggli N, Summerfield A. N(pro) of classical swine fever virus prevents type I interferon-mediated priming of conventional dendritic cells for enhanced interferon-alpha response. J Interferon Cytokine Res (2012) 32:221-9. doi:10.1089/jir.2011.0068
55. Ruggli N, Tratschin JD, Schweizer M, McCullough KC, Hofmann MA, Summerfield A. Classical swine fever virus interferes with cellular antiviral defense: evidence for a novel function of N(pro). J Virol (2003) 77:7645-54. doi:10.1128/JVI.77.13.7645-7654.2003
56. Johns HL, Bensaude E, La Rocca SA, Seago J, Charleston B, Steinbach F, et al. Classical swine fever virus infection protects aortic endothelial cells from pIpC-mediated apoptosis. J Gen Virol (2010) 91:1038-46. doi:10.1099/vir.0.016576-0
57. Doceul V, Charleston B, Crooke H, Reid E, Powell PP, Seago J. The Npro product of classical swine fever virus interacts with IkappaBalpha, the NF-kappaB inhibitor. J Gen Virol (2008) 89:1881-9. doi:10.1099/vir.0.83643-0
58. Tamura T, Nagashima N, Ruggli N, Summerfield A, Kida H, Sakoda Y. Npro of classical swine fever virus contributes to pathogenicity in pigs by preventing type I interferon induction at local replication sites. Vet Res (2014) 45:47. doi:10.1186/1297-9716-45-47
59. Krey T, Bontems F, Vonrhein C, Vaney MC, Bricogne G, Rumenapf T, et al. Crystal structure of the pestivirus envelope glycoprotein E(rns) and mechanistic analysis of its ribonuclease activity. Structure (2012) 20:862-73. doi:10.1016/j.str.2012.03.018
60. Hausmann Y, Roman-Sosa G, Thiel HJ, Rumenapf T. Classical swine fever virus glycoprotein E rns is an endoribonuclease with an unusual base specificity. J Virol (2004) 78:5507-12. doi:10.1128/JVI.78.10.5507-5512.2004
61. Windisch JM, Schneider R, Stark R, Weiland E, Meyers G, Thiel HJ. RNase of classical swine fever virus: biochemical characterization and inhibition by virus-neutralizing monoclonal antibodies. J Virol (1996) 70:352-8
62. Fetzer C, Tews BA, Meyers G. The carboxy-terminal sequence of the pestivirus glycoprotein E(rns) represents an unusual type of membrane anchor. J Virol (2005) 79:11901-13. doi:10.1128/JVI.79.18.11901-11913.2005
63. Tews BA, Schurmann EM, Meyers G. Mutation of cysteine 171 of pestivirus E rns RNase prevents homodimer formation and leads to attenuation of classical swine fever virus. J Virol (2009) 83:4823-34. doi:10.1128/JVI.01710-08
64. Burrack S, Aberle D, Burck J, Ulrich AS, Meyers G. A new type of intracellular retention signal identified in a pestivirus structural glycoprotein. FASEB J (2012) 26:3292-305. doi:10.1096/fj.12-207191
65. Rumenapf T, Unger G, Strauss JH, Thiel HJ. Processing of the envelope glycoproteins of pestiviruses. J Virol (1993) 67:3288-94
66. Iqbal M, Poole E, Goodbourn S, McCauley JW. Role for bovine viral diarrhea virus Erns glycoprotein in the control of activation of beta interferon by double-stranded RNA. J Virol (2004) 78:136-45. doi:10.1128/JVI.78.1.136-145.2004
67. Magkouras I, Matzener P, Rumenapf T, Peterhans E, Schweizer M. RNase-dependent inhibition of extracellular, but not intracellular, dsRNA-induced interferon synthesis by Erns of pestiviruses. J Gen Virol (2008) 89:2501-6. doi:10.1099/vir.0.2008/003749-0
68. Matzener P, Magkouras I, Rumenapf T, Peterhans E, Schweizer M. The viral RNase E(rns) prevents IFN type-I triggering by pestiviral single-and double-stranded RNAs. Virus Res (2009) 140:15-23. doi:10.1016/j.virusres.2008.10.015
69. Zurcher C, Sauter KS, Mathys V, Wyss F, Schweizer M. Prolonged activity of the pestiviral RNase Erns as an interferon antagonist after uptake by clathrin-mediated endocytosis. J Virol (2014) 88:7235-43. doi:10.1128/JVI.00672-14
70. Python S, Gerber M, Suter R, Ruggli N, Summerfield A. Efficient sensing of infected cells in absence of virus particles by plasmacytoid dendritic cells is blocked by the viral ribonuclease E(rns.). PLoS Pathog (2013) 9:e1003412. doi:10.1371/journal.ppat.1003412
71. Meyers G, Saalmuller A, Buttner M. Mutations abrogating the RNase activity in glycoprotein E(rns) of the pestivirus classical swine fever virus lead to virus attenuation. J Virol (1999) 73:10224-35
72. Meyers G, Ege A, Fetzer C, von Freyburg M, Elbers K, Carr V, et al. Bovine viral diarrhea virus: prevention of persistent fetal infection by a combination of two mutations affecting Erns RNase and Npro protease. J Virol (2007) 81:3327-38. doi:10.1128/JVI.02372-06
73. Alves MP, Carrasco CP, Balmelli C, Ruggli N, McCullough KC, Summerfield A. Mycoplasma contamination and viral immunomodulatory activity: dendritic cells open Pandora's box. Immunol Lett (2007) 110:101-9. doi:10.1016/j.imlet.2007.04.006
74. Carrasco CP, Rigden RC, Vincent IE, Balmelli C, Ceppi M, Bauhofer O, et al. Interaction of classical swine fever virus with dendritic cells. J Gen Virol (2004) 85:1633-41. doi:10.1099/vir.0.19716-0
75. Zaffuto KM, Piccone ME, Burrage TG, Balinsky CA, Risatti GR, Borca MV, et al. Classical swine fever virus inhibits nitric oxide production in infected macrophages. J Gen Virol (2007) 88:3007-12. doi:10.1099/vir.0.83042-0
76. Bauhofer O, Summerfield A, McCullough KC, Ruggli N. Role of double-stranded RNA and N(pro) of classical swine fever virus in the activation of monocyte-derived dendritic cells. Virology (2005) 343:93-105. doi:10.1016/j.virol.2005.08.016
77. Schweizer M, Peterhans E. Pestiviruses. Annu Rev Anim Biosci (2014) 2:141-63. doi:10.1146/annurev-animal-022513-114209
78. Husser L, Alves MP, Ruggli N, Summerfield A. Identification of the role of RIG-I, MDA-5 and TLR3 in sensing RNA viruses in porcine epithelial cells using lentivirus-driven RNA interference. Virus Res (2011) 159:9-16. doi:10.1016/j.virusres.2011.04.005
79. Balmelli C, Vincent IE, Rau H, Guzylack-Piriou L, McCullough K, Summerfield A. FcgammaRII-dependent sensitisation of natural interferon-producing cells for viral infection and interferon-alpha responses. Eur J Immunol (2005) 35:2406-15. doi:10.1002/eji.200525998
80. Renson P, Le Dimna M, Keranflech A, Cariolet R, Koenen F, Le Potier MF. CP7_E2alf oral vaccination confers partial protection against early classical swine fever virus challenge and interferes with pathogeny-related cytokine responses. Vet Res (2013) 44:9. doi:10.1186/1297-9716-44-9
81. Renson P, Le Dimna M, Gabriel C, Levai R, Blome S, Kulcsar G, et al. Cytokine and immunoglobulin isotype profiles during CP7_E2alf vaccination against a challenge with the highly virulent Koslov strain of classical swine fever virus. Res Vet Sci (2014) 96:389-95. doi:10.1016/j.rvsc.2014.01.002
82. Franzoni G, Kurkure NV, Edgar DS, Everett HE, Gerner W, Bodman-Smith KB, et al. Assessment of the phenotype and functionality of porcine CD8 T cell responses following vaccination with live attenuated classical swine fever virus (CSFV) and virulent CSFV challenge. Clin Vaccine Immunol (2013) 20:1604-16. doi:10.1128/CVI.00415-13
83. Rau H, Revets H, Cornelis P, Titzmann A, Ruggli N, McCullough KC, et al. Efficacy and functionality of lipoprotein OprI from Pseudomonas aeruginosa as adjuvant for a subunit vaccine against classical swine fever. Vaccine (2006) 24:4757-68. doi:10.1016/j.vaccine.2006.03.028
84. Quesada JR, Talpaz M, Rios A, Kurzrock R, Gutterman JU. Clinical toxicity of interferons in cancer patients: a review. J Clin Oncol (1986) 4:234-43
85. Gillespie JH, Scott FW, Geissinger CM, Czarniecki CW, Scialli VT. Levels of interferon in blood serum and toxicity studies of bacteria-derived bovine alpha I1 interferon in dairy calves. J Clin Microbiol (1986) 24:240-4
86. Mann EA, Markovic SN, Murasko DM. Inhibition of lymphocyte recirculation by murine interferon: effects of various interferon preparations and timing of administration. J Interferon Res (1989) 9:35-51. doi:10.1089/jir.1989.9.35
87. Heikenwalder M, Polymenidou M, Junt T, Sigurdson C, Wagner H, Akira S, et al. Lymphoid follicle destruction and immunosuppression after repeated CpG oligodeoxynucleotide administration. Nat Med (2004) 10:187-92. doi:10.1038/nm987
88. Binder D, Fehr J, Hengartner H, Zinkernagel RM. Virus-induced transient bone marrow aplasia: major role of interferon-alpha/beta during acute infection with the noncytopathic lymphocytic choriomeningitis virus. J Exp Med (1997) 185:517-30. doi:10.1084/jem.185.3.517
89. Chawla-Sarkar M, Lindner DJ, Liu YF, Williams BR, Sen GC, Silverman RH, et al. Apoptosis and interferons: role of interferon-stimulated genes as mediators of apoptosis. Apoptosis (2003) 8:237-49. doi:10.1023/A:1023668705040
90. Durand SV, Hulst MM, de Wit AA, Mastebroek L, Loeffen WL. Activation and modulation of antiviral and apoptotic genes in pigs infected with classical swine fever viruses of high, moderate or low virulence. Arch Virol (2009) 154:1417-31. doi:10.1007/s00705-009-0460-3
91. Li J, Yu YJ, Feng L, Cai XB, Tang HB, Sun SK, et al. Global transcriptional profiles in peripheral blood mononuclear cell during classical swine fever virus infection. Virus Res (2010) 148:60-70. doi:10.1016/j.virusres.2009.12.004
92. Hulst M, Loeffen W, Weesendorp E. Pathway analysis in blood cells of pigs infected with classical swine fever virus: comparison of pigs that develop a chronic form of infection or recover. Arch Virol (2013) 158:325-39. doi:10.1007/s00705-012-1491-8
93. Kaden V, Lange B. Oral immunisation against classical swine fever (CSF): onset and duration of immunity. Vet Microbiol (2001) 82:301-10. doi:10.1016/S0378-1135(01)00400-X
94. Graham SP, Everett HE, Haines FJ, Johns HL, Sosan OA, Salguero FJ, et al. Challenge of pigs with classical swine fever viruses after C-strain vaccination reveals remarkably rapid protection and insights into early immunity. PLoS One (2012) 7:e29310. doi:10.1371/journal.pone.0029310
95. Dewulf J, Laevens H, Koenen F, Mintiens K, de Kruif A. Efficacy of E2-sub-unit marker and C-strain vaccines in reducing horizontal transmission of classical swine fever virus in weaner pigs. Prev Vet Med (2004) 65:121-33. doi:10.1016/j.prevetmed.2004.05.010
96. Piriou L, Chevallier S, Hutet E, Charley B, Le Potiera MF, Albina E. Humoral and cell-mediated immune responses of d/d histocompatible pigs against classical swine fever (CSF) virus. Vet Res (2003) 34:389-404. doi:10.1051/vetres:2003013
97. Graham SP, Haines FJ, Johns HL, Sosan O, La Rocca SA, Lamp B, et al. Characterisation of vaccine-induced, broadly cross-reactive IFN-gamma secreting T cell responses that correlate with rapid protection against classical swine fever virus. Vaccine (2012) 30:2742-8. doi:10.1016/j.vaccine.2012.02.029
98. Tarradas J, Argilaguet JM, Rosell R, Nofrarias M, Crisci E, Cordoba L, et al. Interferon-gamma induction correlates with protection by DNA vaccine expressing E2 glycoprotein against classical swine fever virus infection in domestic pigs. Vet Microbiol (2010) 142:51-8. doi:10.1016/j.vetmic.2009.09.043
99. Franzoni G, Edwards JC, Kurkure NV, Edgar DS, Sanchez-Cordon PJ, Haines FJ, et al. Partial activation of natural killer and gammadelta T cells by classical swine fever viruses is associated with type I interferon elicited from plasmacytoid dendritic cells. Clin Vaccine Immunol (2014) 21:1410-20. doi:10.1128/CVI.00382-14
100. Armengol E, Wiesmuller KH, Wienhold D, Buttner M, Pfaff E, Jung G, et al. Identification of T-cell epitopes in the structural and non-structural proteins of classical swine fever virus. J Gen Virol (2002) 83:551-60
101. Rau H, Revets H, Balmelli C, McCullough KC, Summerfield A. Immunological properties of recombinant classical swine fever virus NS3 protein in vitro and in vivo. Vet Res (2006) 37:155-68. doi:10.1051/vetres:2005049
102. Voigt H, Wienhold D, Marquardt C, Muschko K, Pfaff E, Buettner M. Immunity against NS3 protein of classical swine fever virus does not protect against lethal challenge infection. Viral Immunol (2007) 20:487-94. doi:10.1089/vim.2006.0111
103. Bouma A, de Smit AJ, de Kluijver EP, Terpstra C, Moormann RJ. Efficacy and stability of a subunit vaccine based on glycoprotein E2 of classical swine fever virus 373. Vet Microbiol (1999) 66:101-14. doi:10.1016/S0378-1135(99)00003-6
104. Konig M, Lengsfeld T, Pauly T, Stark R, Thiel HJ. Classical swine fever virus: independent induction of protective immunity by two structural glycoproteins. J Virol (1995) 69:6479-86
105. van Rijn PA, Bossers A, Wensvoort G, Moormann RJ. Classical swine fever virus (CSFV) envelope glycoprotein E2 containing one structural antigenic unit protects pigs from lethal CSFV challenge. J Gen Virol (1996) 77(Pt 11):2737-45. doi:10.1099/0022-1317-77-11-2737
106. Terpstra C, Wensvoort G. The protective value of vaccine-induced neutralising antibody titres in swine fever. Vet Microbiol (1988) 16:123-8. doi:10.1016/0378-1135(88)90036-3
107. Ceppi M, de Bruin MG, Seuberlich T, Balmelli C, Pascolo S, Ruggli N, et al. Identification of classical swine fever virus protein E2 as a target for cytotoxic T cells by using mRNA-transfected antigen-presenting cells. J Gen Virol (2005) 86:2525-34. doi:10.1099/vir.0.80907-0