1. Introduction
Viruses are considered as extremely successful predators as they can replicate and control the host cell synthesizing machinery. Viruses have coevolved with their hosts and thus have limited pathogenicity in any immunocompromised natural host. Viruses can exist in two forms: extra cellular virion particles and intracellular genomes. Virions are more resistant to physical stress than genomes but are susceptible to humoral immune control. Nevertheless, to exist as a species, virus replication and transfer to a new host are essential. These processes are associated with the production of antigenic proteins that make the virus vulnerable to immune control mechanisms ‘warning’ the host of the presence of an invader [1]. There are two classes of viral immunoregulatory proteins: the proteins encoded by genes having sequence similarity with cellular genes and those coded by genes without any sequence similarity to cellular genes. The second class of protein may represent a paradigm for co-evolution [2]. During the period of coexistence with their hosts, viruses have learned how to manipulate host immune control mechanism. It is well established that the viruses have evolved wide variety of immune evasion strategies
2. Newer concepts in the evasion of host deffense by viruses
The main sensors of the innate immune response are pattern recognition receptors (PRR) which can recognize pathogen associated molecular patterns (PAMPs). This recognition leads to the expression of cytokines, chemokines and co-stimulatory molecules that eliminate pathogens like viruses for the activation of antigen presenting cells and for the activation of specific adaptive response [4]. Among the PRRs, there are Toll Like Receptors (TLRs) that can be either endosomal or extracellular [5, 6] and retinoic acid-inducible gene- (RIG-)I/MDA5 (melanoma differentiation-associated gene) [7] known as RNA helicase-like receptors (RLRs). Further, Double-stranded RNA-dependent protein kinase (PKR), 2', 5'-oligoadenylate synthetase (2'- 5' OAS), and adenosine deaminase acting on RNA (ADAR), known as effector proteins, complement the function of PRRs. All these proteins are responsible for recognizing viral components and induce proinflammatory cytokine expression or interferon (IFN) response factors. There are certain cellular components which are manipulated by viruses to evade the innate immune response. Expression of type-I IFN depends on the activation of Interferon Regulatory Factor - 3 (IRF3) and IRF7 via I kappa B kinase (IKK) epsilon and Tank Binding Kinase 1 (TBK1). The genome of Rabies virus, Borna disease virus and Ebola virus code for the P phosphoprotein and VP35 that can block the antiviral response induced by IFN [8, 9, 10]. In contrast, the human herpes simplex virus 8 encodes different analogs of IRF with negative dominant activity, allowing it to interfere with the activity of cellular IRFs [11]. The infected cell polypeptide 0 (ICP0) from Bovine herpes virus can interact with IRF3 and induce its proteasome-dependent degradation [12]. Similarly, the V protein of paramyxoviruses interacts with MD5-α and inhibits IFN-α expression [13].
One of the major non-speific humoral deffense mechanisms of the body for combating and clearing the infectious agents is complement system [14, 15, 16]. Viruses encode homologs of complement regulatory proteins that are secreted and block complement activation and neutralization of virus particles. The cowpox virus (CPV) complement inhibitor, termed inflammation modulatory protein (IMP), blocks immunopathological tissue damage at the site of infection, presumably by inhibiting production of the macrophage chemo attractant factors C3a and C5a. Viruses protect the membranes of infected cells and the lipid envelopes of virus particles from complement lysis by encoding homologs of inhibitors of the membrane-attack complex. Human cytomegalovirus (HCMV), HIV and vaccinia virus (VV) used to borrow different host cellular factors, such as CD59, to protect from complement action. Moreover, some viruses encode Fc receptors [17], thus inducing antibody response. These antibodies may kill infected cells by complement-mediated cytolysis or by antibody-dependent cell-mediated cytotoxicity (ADCC).
In case of FMD virus, following a 5' untranslated region known as the S fragment, there is poly “C” tract comprising over 90 per cent ‘C’ residues [18]. The length of this tract is extremely variable [19]. There are some evidences that length of this tract is associated with virulence and persistence of infections [20].
There is also evidence of viral interference with interferons. Interferons were discovered because of their ability to protect cells from viral infection. The key role of both type I (α and β) and type II (γ) IFNs as one of the first anti-viral defense mechanisms is indicated by the fact that anti-IFN strategies are present in most viruses. Viruses block IFN-induced transcriptional responses and the Janus Kinase (JAK) / signal transducers and activators of transcription (STAT) signal transduction pathways also inhibit the activation of IFN effector pathways that induce an anti-viral state in the cell and limit virus replication. This is mainly achieved by inhibiting double-stranded (ds)-RNA-dependent protein kinase (PKR) activation. Once active, the PKR causes phosphorylation of eukaryotic translation initiation factor 2a (eIF-2a) and the RNase L system, which are responsible for degrading viral RNA and translation in the host cell. Moreover, active PKR is also able to mediate the activation of the transcription factor NFkB which upregulates the expression of interferon cytokines, which work to spread the antiviral signal locally. In addition, active PKR is also able to induce cellular apoptosis. All these mechanisms due to PKR activation ultimately leads to inhibition of the spread of viral infection. But inhibition of PKR activation causes the viral infection to spread and thus helps in evasion of the immune system. Secreted cytokine receptors or binding proteins are mainly encoded by Poxviruses which actually encode soluble versions of receptors for IFN-α and -β (IFN-α/bR) and IFN-γ (IFN-γR), which also block the immune functions of IFNs 6. The IFN-α/βR secreted by Vaccinia virus (VV) is also localized at the cell surface to protect cells from IFN [21, 22]. Additionally, several viruses inhibit the activity of IFN-γ, a key activator of cellular immunity, by blocking the synthesis or activity of factors required for its production, such as interleukin (IL)-18 or IL-12. CPV cytokine response modifier (Crm) A inhibits caspase-1, which processes the mature forms of IL-1b and IL-18 [23]; various poxviruses encode soluble IL-18-binding proteins (IL-18BPs) [24]; measles virus (MeV) binds CD46 in macrophages and inhibits IL-12 production [15]; herpes viruses and poxviruses express IL-10 homologs that diminish the Th1 response by downregulating the production of IL-12 [25, 26].
Cytokines play a key role in the initiation and regulation of the innate and adaptive immune responses, and viruses have learned how to block cytokine production, activity and signal transduction. African swine fever virus (ASFV) replicates in macrophages and encodes an IkB homolog that blocks cytokine expression mediated by nuclear factor (NF)-kB and the nuclear factor activated T cell (NFAT) transcription factors 13. Many viruses block signal transduction by ligands of the tumor necrosis factor (TNF) family, whereas others deliberately induce some cytokine pathways; For example, the Epstein–Barr virus (EBV) latent membrane protein 1 (LMP1) recruits components of the TNF receptor (TNFR) and CD40 transduction machinery to mimic cytokine responses that could be beneficial for the virus, such as cell proliferation [27]. One of the most interesting mechanisms identified in recent years is the mimicry of cytokines (virokines) and cytokine receptors (viroceptors) by large DNA viruses like herpesviruses and poxviruses [28, 29]. The functions of these molecules in the animal host are diverse. Soluble viral cytokine receptors might neutralize cytokine activity and cytokine homologs might redirect the immune response for the benefit of the virus. Alternatively, viruses that infect immune cells might use these homologs to induce signalling pathways in the infected cell that promote virus replication. The herpesvirus cytokine homologs vIL-6 and vIL-17 might have immunomodulatory activity but might also increase proliferation of cells that are targets for viral replication [28]. Viral semaphoring homologs have uncovered a role for the semaphorin family, previously known as chemoattractants or chemorepellents involved in axonal guidance during development in the immune system, and have identified a semaphorin receptor in macrophages that mediates cytokine production [30, 31].
Apoptosis, or programmed cell death, can be triggered by a variety of inducers, including ligands of the TNF family, irradiation, cell cycle inhibitors or infectious agents such as viruses. The cellular proteins implicated in the control of apoptosis are targeted by viral anti-apoptotic mechanisms [32, 33]. Viruses inhibit activation of caspases: encode homologs of the anti-apoptotic protein Bcl-2, block apoptotic signals triggered by activation of TNFR family members by encoding death-effector-domain-containing proteins and inactivate IFN-induced PKR and the tumor suppressor p53, both of which promote apoptosis. Epstein-Barr virus and oncogenic human herpes viruses use Bcl-2 orthologs like BHRF1 and BALF-1 to block mitochondrial release of cytochrome c [34, 35]. Mouse γ- herpesvirus (MHV) -68 encodes a Bcl-2 ortholog (MHVBcl-2) that protects the infected cell against TNF-mediated apoptosis [36]. An alternative mechanism is provided by the glutathione peroxidase of molluscum contagiosum virus (MCV), which provides protection from peroxide or UV induced apoptosis and perhaps from peroxides induced by TNF, macrophages or neutrophils.
Infection with the human and simian immunodeficiency viruses are unique in that the infections give rise to prolonged, continuous viral replication in the infected host. Destruction of virus-specific T helper cells, the emergence of antigenic escape variants and the expression of an envelope complex that structurally minimizes antibody escape to conserved epitopes contribute to persistence. Moreover, the virus encoded protein Nef prevents the viral antigen presentation [37].
3. Recognition of CSFV by immune system
Amidst the diversified mechanisms evolved by different viruses to evade the host immunity (innate or adaptive), CSFV plays a unique role in evading the host deffense and maintain the infection. The virus expresses two major PAMPs: the ssRNA genome and the dsRNA replication intermediates. The TLR’s sensing such patterns are located in the endosomal compartment [38] or in the cytoplasm in case of the cellular helicases Retinoic acid-Inducible Gene 1 (RIG-I) and Melanoma Differentiation-Associated protein 5 (MDA-5) [39]. TLR3 binds dsRNA [40, 41], whereas TLR7 recognizes ssRNA [42, 43]. Conventional DC mainly expresses TLR3 [44] while plasmacytoid DC (pDC) express TLR7 [45]. RIG-I and MDA-5 both bind dsRNA. Recently however it was shown that RIG-I can sense uncapped viral single stranded RNA bearing a 5'-triphosphate [46, 47]. The stimulation of TLR3 leads to the activation of NFkB (early NFkB response) or to the activation of IRF3, which in turn upregulates type I IFN transcription and subsequently transcription of NFkB (late NFkB response) [48]. TLR7 stimulation leads to the activation of IRF7 but not of IRF3 [49]. Thus there is induction of type I interferons and various pro-inflammatory cytokines which play crucial role in antiviral host immune responses. Understimulation of any of these two TLR’s (
4. Few salient features about the disease Classical Swine Fever
Classical swine fever (CSF) is a disease of domestic pigs and wild boar caused by CSF virus (CSFV). CSFV, first reported in the United States in 1833 causes important economical losses worldwide. Besides the United States of America, only Australia, Canada, Ireland, New Zealand, the Scandinavian countries and Switzerland are currently considered free of CSFV. In Europe the recent outbreaks occurred in Bulgaria Croatia and Germany in the year 2006 [50].
The natural reservoir for CSFV is the wild boar, which remains the major threat for new outbreaks. The virus is endemic in most of the Eastern European countries but the domestic pig population of Western Europe can be considered free from the disease. The control measures for CSFV include stamping out with a non-vaccination policy. Consequently pigs have to be free of virus and antibody against CSFV. Whether seroconversion results from vaccination or disease, pigs seropositive for CSFV must be eliminated. Acute or endemic CSF in domestic pigs has large economic impact on general restriction on pig meat trade [51]. The outbreak of CSF, and occurrences of CSFV in the tissues of pigs were reported from India as well [52].
There are three distinct genogroups of the virus (
Early stage of the disease (CSF) is characterized by fever and diarrhoea. The gradual progression of the disease results in a severe wasting syndrome. The terminal stage is signified by a blue discoloration of the skin and weakness of the hind legs along with neurological symptoms. Autopsy finding includes disseminated intravascular coagulopathy, extensive tissue hemorrhages and thymus atrophy [56].
5. A few salient features of the structure, composition and function of the CSFV genome
Classical swine fever virus (CSFV) is a member of the family
CSFV is normally a noncytopathogenic (ncp) virus. A rare cytopathogenic (cp) form can occur spontaneously in cell culture [70] and has also been found in wild boar [71]. Its significance in CSFV pathogenesis is unknown. The CSFV genome consists of single stranded positive sense RNA. This RNA carries a single large open reading frame (ORF) flanked by a 5' and a 3' non-translated region (NTR). The NTR at the 5' end harbours an internal ribosome entry site [72, 73, 74]. Therefore the RNA can directly undergo cap independent translation upon uncoating. The large ORF encodes a single polyprotein which is co and post-translationally cleaved into altogether 12 structural and non-structural proteins including Npro (the first protein encoded by the ORF) by either cellular signalases or viral proteases [75]. It exhibits auto protease activity and cleaves itself from the nascent polyprotein [76]. Npro is the only viral gene that can be deleted without altering virus replication [77]. There is also report of counteraction of the type I IFN induction pathway by Npro [78, 79, 80] by down-regulating the expression levels of the interferon regulatory factor 3 (IRF3) [81, 82]. IRF3 is the rate limiting component of the INF-b promotor enhanceosome and thus regulates the transcriptional activity of this gene [83, 84]. The second protein translated by the ORF is the capsid protein C (Core). It contains the Erns signal sequence [85] and a signalase recognition site [86]. The C gene is followed by the other three structural genes Erns, E1 and E2, the three envelope proteins of CSFV. All these proteins are cleaved by signalases [86]. Erns exists in secreted form [87]. It exhibits RNase activity
6. Npro and its role in induction of poly (IC) induced antiviral activities
The first protein encoded is the non-structural protein Npro. The gene coding for this protein is the only non-essential gene in the pestivirus life cycle [124]. It exhibits autoproteolytical activity and cleaves itself off the downstream nucleocapsid protein C [125, 126, 127]. When CSFV, BVDV and BDV are compared, the amino acid sequence identity of Npro is found to be higher than 70 per cent [128] and the residues Glu22, His49, and Cys69 are essential for the proteiolytic activity of Npro [125]. Moreover, the residues Cys168 and Ser 169 surrounding the cleavage sites are also conserved [126]. Resistance to poly(IC)-induced cell death and control of IFN induction are dependent on the presence of the Npro gene, indicating a function of Npro in innate immune evasion of CSFV [129]. The characterisation of Npro gene is also found to be beneficial for the development of inactivated vaccine [130].
7. Immune evasion and immunopathogenesis of CSF
CSF virus (CSFV) has high affinity for vascular endothelial cells and lymphoreticular cells including T cells, B cells and monocytes [122]. Severe depletion of B cells and T cells in Peripheral Blood Mononuclear Cells (PBMC) and virus persistence in lymphoid tissues is thought to be the most important characteristics of CSFV infection that leads to the acquired immunosuppressive state [131, 132].
Recently it has been observed that ncp BVDV induces translocation of IRF-3 into the nucleus without subsequent binding to DNA [133]. Furthermore, ncp BVDV was able to block Semliki Forest virus-induced IFN production through a block in the formation of IRF-3 – DNA complexes [134]. Whether this is also true for CSFV and whether Npro is involved in this process remain to be investigated. But we can not ignore the fact that the presence of Npro permits efficient infection of monocytic cells, including monocytes, macrophages, and even dendritic cells.These cells are among the main targets for CSFV allowing high-level replication and permit cell-associated spreading and colonization of immunological tissue by CSFV. Furthermore, they appear to play a central role in virus-induced immunomodulation [135].
Dendritic cells (DCs) are one of the primary immunological sentinels of the immune system [136, 137]. Their strategic localization at mucosal surfaces and dermal layers makes them an early target for virus contact [138]. Functional disruption of DCs is an important strategy for viral pathogens to evade host defences [139, 140]. Monocytotropic viruses such as CSFV can employ such a mechanism as the virus can suppress immune responses and induce apoptosis without infecting lymphocytes. The virus infects both conventional dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs) [141, 142, 143]. The infected DCs display neither modulated MHC nor CD80/86 expression. Interestingly, similar to macrophages, CSFV do not induce IFN-α responses in the cDCs as Npro protein promotes proteosomal degradation of interferon regulatory factor (IRF) 3 [144, 145]. So, it can be said that CSFV can replicate in cDCs and control type I IFN responses, without interfering with the immune reactivity [146]. However, in pDCs, IRF 7 is more prominent and there is lack of interference of Npro with IRF 3 which results in augmented IFN α response by pDCs. This is the reason for an exaggerated pDC response, relating to the immunopathological characteristics of the disease [147, 148, 149].
Regulation of CSFV RNA turnover with minimal accumulation of dsRNA is an important factor governing the evasion of host deffense by the virus [144]. The temporal modulation of xlink-3 processing by the xlink autoprotease is crucial in RNA replication control and the intracellular level of NS3 strictly correlates with the efficiency of RNA replication [150]. But, whether these proteins regulate the dsRNA levels remains to be established. The viral structural protein Erns is also actively involved in the dsRNA-mediated induction of IFNβ [151].
IL-6 is an important cytokine in providing protection during early part of CSFV infection. The synthesis of NS4B protein during viral replication in the tonsil down regulates the expression of IL-6 and this is especially true with CSFV strain Brescia [123]. Swine Leukocyte Antigen I (SLA I) molecules present the endogenous peptides to activate the CD8+ T cells that control viral replication within cells. CSFV interferes with the expression of SLA I molecules by the monocytic cells, thereby, inhibiting apoptosis of the cells. This strategy seems to be quiet helpful for the virus to escape the host immuno-surveillance and establishment of persistence in tissues [152]. Antibodies may be temporarily detected in serum sample. But these antibodies can not eliminate the virus from the host system. Consequently, the antibodies are neutralized by the virus and cease to be detectable [153].
Blocking B-lymphocyte maturation by infection and destruction of germinal centers is a key event in the pathogenesis of acute, lethal CSF before the development of generalized infection [154]. Immature B lymphocytes (
8. Conclusion
The understanding of the virus-host interaction network is important to design antiviral strategies and to formulate antiviral drugs. In this context, the ability of the viruses to evade the host immune system plays a key role. The understanding of the complex mechanisms of host immune system manipulation will ultimately result in undertaking suitable immunoprohylactic measures.
References
- 1.
Pulendran B Palucka K Banchereau J 2001 Sensing pathogens and tuning immune responses Sci.,293 253 256 - 2.
MacLachlan N. J. and Dubovi, E. J. Fenner’s Veterinary Virology. 4th Edition. - 3.
Medical Virology. 4th Edition. andWhite D. O Fenner F. J - 4.
Pedraza S. T andBetancur J. G Urcuqui-inchima S 2010 Viral recognition by the innate immune system: the role of pattern recognition receptors Colomb. Med.,41 4 377 387 - 5.
andJaneway C Medzhitov R 2000 Viral interference with IL-1 and toll signallin g. Proc. Natl. Acad. Sci.,97 10682 10683 - 6.
Netea M. G Van Der Graaf C andVan Der Meer J. W Kullberg B. J 2004 Toll-like receptors and the host defense against microbial pathogens: bringing specificity to the innate-immune system. J. Leukoc. Biol.,75 749 755 - 7.
Kang J. Y Nan X Jin M. S Youn S. J andRyu Y. H Mah S 2009 Recognition of lipopeptide patterns by Toll-like receptor 2- Toll-like receptor 6 heterodime r.31 873 884 - 8.
Brzozka K andFinke S Conzelmann K. K 2005 Identification of the rabies virus alpha/beta interferon antagonist: phosphoprotein P interferes with phosphorylation of interferon regulatory factor 3. J. Virol.,79 7673 7681 - 9.
Conzelmann K. K 2005 Transcriptional activation of alpha/beta interferon genes: interference by non-segmented negative strand RNA viruses. J. Virol.,79 5241 5248 - 10.
35 protein of Ebola virus inhibits the antiviral effect mediated by double-stranded RNA-dependent protein kinase PKR. J. Virol., .,Feng ,Z .,Cerveny ,M . andYan ,Z . (He ,B 2007 ).The VP 81 182 192 . - 11.
Lin R Genin P Mamane Y Sgarbanti M andBattistini A Harrington W. J 2001 HHV-8 encoded vIRF-1 represses the interferon antiviral response by blocking IRF-3 recruitment of the CBP/300 co activators. Oncogene. 20: 800-11. - 12.
Saira K andZhou Y Jones C 2007 The infected cell protein 0 encoded by bovine herpesvirus 1 (bICP0) induces degradation of interferon response factor 3 and, consequently, inhibits beta interferon promoter activity. J. Virol.,81 3077 3086 - 13.
Andrejeva J Childs K. S Young D. F Carlos T. S andStock N Goodbourn S 2004 The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN-beta promo ter. Proc. Natl. Acad. Sci.,101 17264 17269 - 14.
Smith G. L Symons J. A Khanna A andVanderplasschen A Alcami A 1997 Vaccinia virus immune evasion. Immunol. Rev.,159 137 154 - 15.
Tortorella D Benjamin E. G Margo H. F andDanny J. S Hidde L. P 2000 Viral subversion of the immune system. Annu. Rev. Immunol.,18 861 926 - 16.
Kotwal G. J 2000 Poxviral mimicry of complement and chemokine system components: what’s the end game? Immunol. Today21 242 248 - 17.
Kalvakolanu D. V 1999 Virus interception of cytokine-regulated pathways. Trends Microbiol.,7 166 171 - 18.
Longjam N Deb R Sarmah A. K Tayo T andAwachat V. B Saxena V. K 2011 A brief review on diagnosis of Foot-and-Mouth disease of livestock: Conventional to molecular tools. Vet. Med. Int.,1 17 - 19.
Giomi M. P. C andBergmann I. E Scodeller E. A 1984 Heterogeneity of the polyribocytidylic acid tract in aphthovirus: biochemical and biological studies of viruses carrying polyribocytidylic acid tracts of different lengths. J. Virol.,51 799 805 - 20.
andHarris T. J. R Brown F 1977 Biochemical analysis of a virulent and an avirulent strain of foot and mouth disease virus. J. Gen. Virol.,34 1 87 105 - 21.
Smith G. L andSymons J. A Alcami A 1998 Poxviruses: interfering with interferons. Sem. Virol.,8 409 418 - 22.
Goodbourn S andDidcock L Randall R. E 2000 Interferons: cell signalling, immune modulation, antiviral responses and virus countermeasures. J. Gen. Virol.,81 2341 2364 - 23.
and inhibition of interferon gamma induction by human poxvirus-encoded proteins. Proc. Natl. Acad. Sci., andXiang Y Moss B 1999 I. L Binding 96 11537 11542 - 24.
Born T. L Morrison L. A Esteban D. J Vandenbos T Thebeau L. G Chen N Spriggs M. K andSims J. E Buller R. M. L 2000 A poxvirus protein that binds to and inactivates IL-18 and inhibits NK cell response. J. Immunol.,164 3246 3254 - 25.
Spriggs M. K 1996 One step ahead of the game: viral immunomodulatory molecules. Annu. Rev. Immunol.,14 101 130 - 26.
Kotenko S. V Saccani S Izotova L. S andMirochnitchenko O. V Pestka S 2000 Human cytomegalovirus harbors its own unique IL-10 homolog (cmvIL-10). Proc. Natl. Acad. Sci., U. S. A.97 1695 1700 - 27.
Farrell P. J 1998 Signal transduction from the Epstein-Barr virus LMP-1 transforming protein. Trends. Microbiol.,6 175 177 - 28.
Nash P andBarrett J Cao J. X 1999 Immunomodulation by viruses: the myxoma virus story. Immunol. Rev.,168 103 120 - 29.
Lalani A. S andBarrett J. W Mcfadden G 2000 Modulating chemokines: more lessons from viruses. Immunol. Today21 100 106 - 30.
Spriggs M. K 1999 Shared resources between the neural and immune systems: semaphorins join the ranks. Curr. Opin. Immunol.,11 387 391 - 31.
andAlcami A Koszinowski U. H 1998 Poxviruses: capturing cytokines and chemokines. Sem. Virol.,8 419 427 - 32.
andTurner P. C Moyer R. W 1998 Control of apoptosis by poxviruses. Sem. Virol.,8 453 469 - 33.
andEverett H Mcfadden G 1999 Apoptosis: an innate immune response to virus infection. Trends Microbiol.,7 160 165 - 34.
Henderson S 1993 Epstein-Barr virus-coded BHRF I protein, a viral homologue of Bcl-2, protect human B cells from programmed cell death. Proc. Natl. Acad. Sci.,90 8479 8483 - 35.
Marshall W. L Datta R Hanify K andTeng E Finberg R. W 1999 U937 cells over expressing bcl-xl are resistant to human immunodefficiency virus-I induced apoptosis and human immunodeficiency virus-I replication. Virol.,256 1 7 - 36.
Benedict C. A andNorris P. S Ware C. F 2002 To kill or be killed: viral evasion of apoptosis. Nature.3 11 1013 1018 - 37.
andJohnson W. E Desrosiers R. C 2002 Viral Persistence: HIV’s strategies of immune system evasion. Annu. Rev. Med.,53 499 518 - 38.
andKawai T Akira S 2006 TLR signalling. Cell Death. Differ.,13 816 825 - 39.
Yoneyama M Kikuchi M Matsumoto K Imaizumi T Miyagishi M Taira K Foy E Loo Y. M Gale M Akira S Yonehara S andKato A Fujita T 2005 Shared and Unique Functions of the DExD/H-Box Helicases RIG-I, MDA5, and LGP2 in Antiviral Innate Immunity. J. Immunol.,175 2851 2858 - 40.
Matsumoto M Funami K andOshiumi H Seya T 2004 Toll-like receptor 3: A link between toll-like receptor, interferon and viruses. Microbiol. Immunol.,48 147 154 - 41.
andSen G. C Sarkar S. N 2005 Transcriptional signaling by double-stranded RNA: role of TLR3. Cytokine Growth Factor Rev.,16 1 14 - 42.
andCrozat K Beutler B 2004 TLR7: A new sensor of viral infection. Proc. Nat. Acad. Sci.,101 6835 6836 - 43.
Diebold S. S Kaisho T Hemmi H andAkira S Sousa C. R. E 2004 Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Scie.,303 1529 1531 - 44.
Visintin A Mazzoni A Spitzer J. H Wyllie D. H andDower S. K Segal D. M 2001 Regulation of Toll-like receptors in human monocytes and dendritic cells. J. Immunol.,166 249 255 - 45.
Ito T andWang Y. H Liu Y. J 2005 Plasmacytoid dendritic cell precursors/type I interferon producing cells sense viral infection by Toll-like receptor (TLR) 7 and TLR9. Springer Semin. Immunopathol.,26 221 229 - 46.
Hornung V Ellegast J Kim S Brzozka K Jung A Kato H Poeck H Akira S Conzelmann K. K Schlee M andEndres S Hartmann G 2006 Triphosphate RNA is the ligand for RIG-I. Scie.,314 994 997 - 47.
Pichlmair A Schulz O Tan C. P Naslund T. I Liljestrom P andWeber F Reis S 2006 RIG-I-mediated antiviral responses to single-stranded RNA bearing 5’-phosphates. Scie.,314 997 1001 - 48.
andAkira S Hemmi H 2003 Recognition of pathogen-associated molecular patterns by TLR family. Immunol. Lett.,85 85 95 - 49.
Kawai T Sato S Ishii K. J Coban C Hemmi H Yamamoto M Terai K Matsuda M Inoue J Uematsu S andTakeuchi O Akira S 2004 Interferon-alpha induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6. Nat. Immunol.,5 1061 1068 - 50.
andRuggli N Summerfield A 2007 Characterization of immune evasion strategies of classical swine fever virus in monocytic and dendritic cells. Ph.D thesis, Institute of Virology and Immunoprophylaxis, Mittelhausern, Switzerland. - 51.
http://www oie.int/wahid. - 52.
andSarma D. K Bostami B 2008 Isolation and growth characteristics of classical swine fever in PK-15 cell line. J. Appl. Biosci. Biotech.,3 29 32 - 53.
Lowings P Ibata G andNeedham J Paton D 1996 Classical swine fever virus diversity and evolution. J. Gen. Virol.,77 1311 1321 - 54.
GreiserWilke, I., Parchariyanon, S., Song, J. Y., Liou, P. P., Stadejek, T., Lowings, J. P., Bjorklund, H. and Belak, S. (Paton D. J Mcgoldrick A 2000 Genetic typing of classical swine fever virus. Vet. Microbiol.,73 137 157 - 55.
Chandra Naik, B. M., Rathnamma, D., Isloor, S., Venkatesha, M. D., Leena, G., Veeresh, H. and Patil, S. S. (Chakraborty S Veeregowda B. M 2011 Molecular characterization and genogrouping of classical sine fever virus isolated from field outbreaks. Ind. J. Anim. Sci.,81 8 803 806 - 56.
Trautwein G 1988 Pathology and pathogenesis of the disease,27 53 In B. Liess (ed.), Classical swine fever and related viral infections. Martinus Nijhoff Publishing, Boston. - 57.
Fauquet C. M Mayo M. A Maniloff J andDesselberger U Ball L. A 2005 Virus Taxonomy. Eighth Report of the International Committee on Taxonomy of Viruses. Academic Press, SanDiego. - 58.
Moennig V andFloegel-niesmann G Greiser-wilke I 2003 Clinical signs and epidemiology of classical swine fever: a review of new knowledge. Vet J.,165 1 11 20 - 59.
Sizova D. V Kolupaeva V. G Pestova T. V andShatsky I. N Hellen C. U. T 1998 Specific interaction eukaryotic translation initiation factor 3 with the 5’ non translated regions of Hepatitis C virus and Classical Swine Fever Virus RNAs. J. Virol.,72 6 4775 4782 - 60.
andFletcher S. P Jackson R. J 2002 Pestivirus Internal Ribosome Entry Site (IRES) structure and function: Elements in the 5’ untranslated region important for IRES function. J. Virol.,76 5024 5033 - 61.
Vanderhallen H Mittelholzer C andHofmann M. A Koenen F 1999 Classical swine fever virus is genetically stable in vitro and in vivo. Arch. Virol.,144 9 1669 1677 - 62.
He D. M Qian K. X Shen G. F Zhang Z. F Li Y. N andSu Z. L Shao H. B 2007 Recombination and expression of classical swine fever virus (CSFV) structural protein E2 gene in Chlamydomonas reinhardtii chloroplasts. Colloids and Surfaces B: Biointerfaces.,55 1 26 30 - 63.
Rümenapf T Unger G andStrauss J. H Thiel H. J 1993 Processing of the envelope glycoproteins of pestiviruses. J. Virol.,67 3288 3294 - 64.
Falgout B andPethel M Zhang Y. M 1995 Flaviviridae: The viruses and their replication. J. Virol.,69 11 7232 7243 - 65.
Elbers A. R. W Stegeman A Moser H Ekker H. M andSmak J. A Pluimers F. H 1999 The classical swine fever epidemic197 1998 in the Netherlands: descriptive epidemiology. Preventive Vet. Med., 42(3-4): 157-184. - 66.
Heimann M Roman-sosa G Martoglio B andThiel H. J Rümenapf T 2006 Core protein of pestiviruses is processed at the C terminus by signal peptide peptidase. J. Virol.,80 1915 1921 - 67.
Thiel H. J Stark R Meyers G andWeiland E Rumenapf T 1991 Proteins encoded in the 5´ region of the pestivirus genome- considerations concerning taxonomy. Vet. Microbiol.,33 213 219 - 68.
König M Lengsfeld T Pauly T andStark R Thiel H. J 1995 Classical swine fever virus: independent induction of protective immunity by two structural glycoproteins. J. Virol.,69 10 6479 6486 - 69.
Stark R Rümenapf T andMeyers G Thiel H. J 1990 Genomic localization of hog cholera virus glycoproteins. Virol.,174 286 289 - 70.
Mittelholzer C Moser C andTratschin J. D Hofmann M. A 2000 Analysis of classical swine fever virus replication kinetics allows differentiation of highly virulent from avirulent strains. Vet. Microbiol.,74 4 293 308 - 71.
Aoki H Ishikawa K Sakoda Y Sekiguchi H Kodama M andSuzuki S Fukusho A 2001 Characterization of classical swine fever virus associated with defective interfering particles containing a cytopathogenic subgenomic RNA isolated from wild boar. J. Vet. Med. Sci.,63 751 758 - 72.
andFletcher S. P Jackson R. J 2002 Pestivirus Internal Ribosome Entry Site (IRES) structure and function: Elements in the 5’ untranslated region important for IRES function. J. Virol.,76 5024 5033 - 73.
Kolupaeva V. G andPestova T. V Hellen C. U 2000 Ribosomal binding to the internal ribosomal entry site of classical swine fever virus. RNA.6 1791 1807 - 74.
P. J., van der,Rijnbrand R S. T Van Rijn P. A Spaan W. J Bredenbeek 1997 Internal entry of ribosomes is directed by the 5’ noncoding region of classical swine fever virus and is dependent on the presence of an RNA pseudoknot upstream of the initiation codon. J. Virol.,71 451 457 - 75.
andLindenbach B. D Rice C. M 2001 Flaviviridae: the viruses and their replication. In: D. M. Knipe, P. M. Howley, D. E. Griffin, R. A. Lamb, M. A. Martin, B. Roizman, S. E. Straus (Eds.), Fields Virology. Lippincott Williams & Wilkins, Philadelphia,991 1041 - 76.
Rümenapf T Stark R andHeimann M Thiel H. J 1998 N-terminal protease of pestiviruses: identification of putative catalytic residues by site-directed mutagenesis. J. Virol.,72 2544 2547 - 77.
Tratschin J. D Moser C andRuggli N Hofmann M. A 1998 Classical swine fever virus leader proteinase Npro is not required for viral replication in cell culture. J. Virol.,72 7681 7684 - 78.
Basler C. F Garcia-sastre A 2002 Viruses and the type I interferon antiviral system: induction and evasion. Int. Rev. Immunol.,21 305 337 - 79.
Ruggli N Tratschin J. D Schweizer M Mccullough K. C andHofmann M. A Summerfield A 2003 Classical swine fever virus interferes with cellular antiviral defense: evidence for a novel function of Npro. J. Virol.,77 7645 7654 - 80.
Ruggli N Bird B. H Liu L Bauhofer O andTratschin J. D Hofmann M. A 2005 Npro of classical swine fever virus is an antagonist of double-stranded RNA-mediated apoptosis and IFN-alpha/beta induction. Virology340 265 276 - 81.
Hilton L Moganeradj K Zhang G Chen Y. H Randall R. E andMccauley J. W Goodbourn S 2006 The Npro product of bovine viral diarrhoea virus inhibits DNA binding by interferon regulatory factor 3 and targets it for proteasomal degradation. J. Virol.,80 11723 11732 - 82.
La Rocca S. A., Herbert, R. J., Crooke, H., Drew, T. W., Wileman, T. E. and Powell, P. P. (2005 Loss of interferon regulatory factor 3 in cells infected with classical swine fever virus involves the N-terminal protease, Npro. J. Virol.,79 7239 7247 - 83.
Maniatis T Falvo J. V Kim T. H Kim T. K Lin C. H Parekh B. S Wathelet M. G 1998 Structure and function of the interferon-beta enhanceosome. Cold Spring Harb. Symp. Quant. Biol.,63 609 620 - 84.
andMerika M Thanos D 2001 Enhanceosomes. Curr. Opin. Genet. Dev.,11 205 208 - 85.
Rümenapf T Unger G andStrauss J. H Thiel H. J 1993 Processing of the envelope glycoproteins of pestiviruses. J. Virol.,67 3288 3294 - 86.
Heimann M Roman-sosa G Martoglio B Thiel H. J Rümenapf T 2006 Core protein of pestiviruses is processed at the C terminus by signal peptide peptidase. J. Virol.,80 1915 1921 - 87.
Bruschke C. J Hulst M. M Moormann R. J andVan Rijn P. A Van Oirschot J. T 1997 Glycoprotein Erns of pestiviruses induces apoptosis in lymphocytes of several species. J. Virol.,71 6692 6696 - 88.
RomanSosa, G., Thiel, H. J. and Rümenapf, T. (Hausmann Y 2004 Classical swine fever virus glycoprotein E-rns is an endoribonuclease with an unusual base specificity. J. Virol.,78 5507 5512 - 89.
Iqbal M Poole E andGoodbourn S Mccauley J. W 2004 Role for bovine viral diarrhea virus Erns glycoprotein in the control of activation of beta interferon by double-stranded RNA. J. Virol.,78 136 145 - 90.
E. M. (Meyers G Ege A von,Fetzer C F. M Elbers K Carr V Prentice H Charleston B andSchurmann 2007 Bovine viral diarrhoea virus: Prevention of persistent foetal infection by a combination of two mutations affecting the Erns RNase and the Npro protease. J. Virol.,81 3327 3338 - 91.
Van Rijn P. A Miedema G. K Wensvoort G andVan Gennip H. G Moormann R. J 1994 Antigenic structure of envelope glycoprotein E1 of hog cholera virus. J. Virol.,68 3934 3942 - 92.
Van Rijn P. A Bossers A andWensvoort G Moormann R. J 1996 Classical swine fever virus (CSFV) envelope glycoprotein E2 containing one structural antigenic unit protects pigs from lethal CSFV challenge. J. Gen. Virol.,77 2737 2745 - 93.
Harada T andTautz N Thiel H. J 2000 E2-7 region of the bovine viral diarrhea virus polyprotein: Processing and functional studies. J. Virol., 74: 9498-9506. - 94.
Pavlovic D Neville D. C Argaud O Blumberg B Dwek R. A andFischer W. B Zitzmann N 2003 The hepatitis C virus7 protein forms an ion channel that is inhibited by long-alkyl chain iminosugar derivatives. Proc. Natl. Acad. Sci. U. S. A., 100: 6104-6108. - 95.
Lackner T Muller A Pankraz A Becher P Thiel H. J Gorbalenya A. E Tautz N 2004 Temporal modulation of an autoprotease is crucial for replication and pathogenicity of an RNA virus. J. Virol.,78 10765 10775 - 96.
Tautz N Elbers K Stoll D andMeyers G Thiel H. J 1997 Serine protease of pestiviruses: determination of cleavage sites. J. Virol.,71 5415 5422 - 97.
Tautz N andKaiser A Thiel H. J 2000 NS3 serine protease of bovine viral diarrhea virus: Characterization of active site residues, NS4A cofactor domain, and protease-cofactor interactions. Virol.,273 351 363 - 98.
Xu J Mendez E Caron P. R Lin C Murcko M. A andCollett M. S Rice C. M 1997 Bovine viral diarrhea virus NS3 serine proteinase: polyprotein cleavage sites, cofactor requirements, and molecular model of an enzyme essential for pestivirus replication. J. Virol.,71 5312 5322 - 99.
Lackner T Muller A Pankraz A Becher P Thiel H. J andGorbalenya A. E Tautz N 2004 Temporal modulation of an autoprotease is crucial for replication and pathogenicity of an RNA virus. J. Virol.,78 10765 10775 - 100.
Lackner T Muller A Konig M andThiel H. J Tautz N 2005 Persistence of bovine viral diarrhea virus is determined by a cellular cofactor of a viral autoprotease. J. Virol.,79 9746 9755 - 101.
is required for production of infectious bovine viral diarrhea virus. J. Virol.,Agapov E. V Murray C. L Frolov I Qu L andMyers T. M Rice C. M 2004 Uncleaved N. S 78 2414 2425 - 102.
Moulin H. R Seuberlich T Bauhofer O Bennett L. C Tratschin J. D andHofmann M. A Ruggli N 2007 Nonstructural proteins NS2 3 and NS4A of classical swine fever virus: essential features for infectious particle formation. Virology in press. - 103.
Mackintosh S. G Lu J. Z Jordan J. B Harrison M. K Sikora B Sharma S. D Cameron C. E andRaney K. D Sakon J 2006 Structural and biological identification of residues on the surface of NS3 helicase required for optimal replication of the hepatitis C virus. J. Biol. Chem.281 3528 3535 - 104.
Sampath A Xu T Chao A Luo D andLescar J Vasudevan S. G 2006 Structure-based mutational analysis of the NS3 helicase from dengue virus. J. Virol.,80 6686 6690 - 105.
Grassmann C. W andIsken O Behrens S. E 1999 Assignment of the multifunctional NS3 protein of bovine viral diarrhea virus during RNA replication: an in vivo and in vitro study. J. Virol.,73 9196 9205 - 106.
and Del Vecchio, A. M. (Gu B Liu C Lin-goerke J Maley D. R Gutshall L. L Feltenberger C. A 2000 The RNA helicase and nucleotide triphosphatase activities of the bovine viral diarrhea virus NS3 protein are essential for viral replication. J. Virol.,74 1794 1800 - 107.
Xu J Mendez E Caron P. R Lin C Murcko M. A andCollett M. S Rice C. M 1997 Bovine viral diarrhea virus NS3 serine proteinase: polyprotein cleavage sites, cofactor requirements, and molecular model of an enzyme essential for pestivirus replication. J. Virol.,71 7 5312 5322 - 108.
Zhang P Xie J Yi G andZhang C Zhou R 2005 De novo RNA synthesis and homology modeling of the classical swine fever virus RNA polymerase. Virus Res.,112 9 23 - 109.
Grummer B andGrotha S Greiser-wilke I 2004 Bovine viral diarrhoea virus is internalized by clathrin-dependent receptor-mediated endocytosis. J. Vet. Med. B Infect. Dis. Vet. Public Health.,51 427 432 - 110.
Krey T andThiel H. J Rümenapf T 2005 Acid-resistant bovine pestivirus requires activation for pH-triggered fusion during entry. J. Virol.,79 4191 4200 - 111.
Krey T Moussay E andThiel H. J Rümenapf T 2006 Role of the low-density lipoprotein receptor in entry of bovine viral diarrhea virus. J. Virol.,80 10862 10867 - 112.
a cellular receptor for bovine viral diarrhea virus. J. Virol.,Maurer K Krey T Moennig V andThiel H. R Rümenapf T 2004 C. D Is 78 1792 1799 - 113.
andHulst M. M Moormann R. J 1997 Inhibition of pestivirus infection in cell culture by envelope proteins E (rns) and E2 of classical swine fever virus: E (rns) and E2 interact with different receptors. J. Gen. Virol.,78 2779 2787 - 114.
Wang Z Nie Y. C Wang P. G andDing M. X Deng H. K 2004 Characterization of classical swine fever virus entry by using pseudotyped viruses: E1 and E2 are sufficient to mediate viral entry. Virol.,330 332 341 - 115.
Quinkert D andBartenschlager R Lohmann V 2005 Quantitative analysis of the hepatitis C virus replication complex. J. Virol.,79 13594 13605 - 116.
Salonen A andAhola T Kaariainen L 2005 Viral RNA replication in association with cellular membranes. Curr. Top. Microbiol. Immunol.,285 139 173 - 117.
Westaway E. G andMackenzie J. M Khromykh A. A 2003 Kunjin RNA replication and applications of Kunjin replicons. Adv. Virus Res.,59 99 140 - 118.
Moulin H. R Seuberlich T Bauhofer O Bennett L. C Tratschin J. D andHofmann M. A Ruggli N 2007 Nonstructural proteins NS2 3 and NS4A of classical swine fever virus: essential features for infectious particle formation. Virol., in press. - 119.
Hu°gle T., F. Fehrmann, E., B., Kohara, M., Krausslich, H. G., Rice, C. M., Blum, H. E. Moradpour, D. (2001 The hepatitis C virus non-structural protein 4B is an integral endoplasmic reticulum membrane protein. Virol.,284 70 81 - 120.
Lundin M Lindstrom H andGronwall C Persson M. A 2006 Dual topology of the processed hepatitis C virus protein NS4B is influenced by the NS5A protein. J. Gen. Virol.,87 3263 3272 - 121.
Lundin M Monne M Widell A andVon Heijne G Persson M. A 2003 Topology of the membrane-associated hepatitis C virus protein NS4B. J. Virol.,77 5428 5438 - 122.
Qu L andMcmullan L. K Rice C. M 2001 Isolation and characterization of noncytopathic pestivirus mutants reveals a role for nonstructural protein NS4B in viral cytopathogenicity. J. Virol.,75 10651 10662 - 123.
M.Fernandez-sainz D. P Gladue L. G Holinka L. G O Donnell V Gudmundsdottir I Prarat M. V Patch J. R Golde W. T Lu Z Zhu J Carrillo C Risatti G. R andBorca 2010 Mutations in Classical Swine Fever Virus NS4B affect virulence in swine. J. Virol., 84(3): 1536-1549. - 124.
Lai V. C. H Zhong W. D Skelton A Ingravallo P Vassilev V Donis R. O Hong Z Lau J. Y. N 2000 Generation and characterization of a hepatitis C virus NS3 protease-dependent bovine viral diarrhea virus. J. Virol.,74 6339 6347 - 125.
Rumenapf T Stark R andHeimann M Thiel H. J 1998 N-terminal protease of pestiviruses: identification of putative catalytic residues by site directed mutagenesis. J. Virol.,72 2544 2547 - 126.
Stark R Meyers G andRumenapf T Thiel H. J 1993 Processing of pestivirus polyprotein: cleavage site between autoprotease and nucleocapsid protein of classical swine fever virus. J. Virol.,67 7088 7095 - 127.
R. H. (Zhou A Der,Paranjape J. M S. D Williams B. R andSilverman 1999 Interferon action in triply deficient mice reveals the existence of alternative antiviral pathways. Virol.,258 435 440 - 128.
Roehe P. M andWoodward M. J Edwards S 1992 Characterisation of20 gene sequences from a border disease-like pestivirus isolated from pigs. Vet. Microbiol., 33: 231-238. - 129.
Ruggli N Tratshin J. D Schweizer M Mccullough K. C andHofmann M. A Summerfield A 2003 Classical Swine Fever Virus interferes with Cellular Antiviral Defense: Evidence for a Novel Function of Npro. J. Virol.,77 7645 7654 - 130.
Chandranaik B. M Renukaprasad C Patil S. S Venkatesha M. D Giridhar P andByregowda S. M Prabhudas K 2011 Development of cell culture based inactivated Classical swine fever vaccine. Ind. Vet. J.,88 4 16 18 - 131.
Summerfield A Hofmann M. A Mccullough K. C 1998a Low density blood granulocytic cells induced during classical swine fever are targets for virus infection. Vet. Immunol. Immunopathol.,63 289 301 - 132.
Ambagala A. P andSolheim J. C Srikumaran S 2005 Viral interference with MHC class I antigen presentation pathway: the battle continues. Vet. Immunol. Immunopathol.,107 1 15 - 133.
Schweizer M Peterhans E 2001 Noncytopathic bovine viral diarrhea virus inhibits double-stranded RNA-induced apoptosis and interferon synthesis. J. Virol.,75 4692 4698 - 134.
Baigent S. J Zhang G Fray M. D Flick-smith H andGoodbourn S J. W Mccauley 2002 Inhibition of beta interferon transcription by non-cytopathogenic bovine viral diarrhea virus is through an interferon regulatory factor 3-dependent mechanism. J. Virol.,76 8979 8988 - 135.
Knoetig S. M Summerfield A andSpagnuolo-weaver M Mccullough K. C 1999 Immunopathogenesis of classical swine fever: role of monocytic cells. Immunol.,97 359 366 - 136.
Banchereau J Briere F Caux C Davoust J Lebecque S Liu Y. J andPulendran B Palucka K 2000 Immunobiology of dendritic cells. Annu. Rev. Immunol.,18 767 811 - 137.
Steinman R. M 1991 The dendritic cell system and its role in immunogenicity. Annu. Rev. Immunol.,9 271 296 - 138.
Pulendran B andPalucka K Banchereau J 2001 Sensing pathogens and tuning immune responses. Sci.,293 253 256 - 139.
Van Oirschot J. T De Jong D Huffels N. D 1983 Effect of infections with swine fever virus on immune functions. II. Lymphocyte response to mitogens and enumeration of lymphocyte subpopulations. Vet. Microbiol.,8 81 95 - 140.
Steinman R. M 1991 The dendritic cell system and its role in immunogenicity. Annu. Rev. Immunol.,9 271 296 - 141.
Summerfield A Guzylack-piriou L Schaub A Carrasco C. P Tache V Charley B 2003 Porcine peripheral blood dendritic cells and natural interferon-producing cells. Immunol.,110 440 449 - 142.
Trautwein G 1988 Pathology and pathogenesis of the disease. In Classical Swine Fever and Related Infections,27 54 Edited by B. Liess. Boston: Martinus Nijhoff Publishing. - 143.
Mccullough K. C andRuggli N Summerfield A 2009 Dendritic cells- At the front-line of pathogen attack. Vet. Immunol. Sympos., 128(1-3): 7-15. - 144.
Bauhofer O Summerfield A andMccullough K. C Ruggli N 2005 Role of double-stranded RNA and Npro of classical swine fever virus in the activation of monocyte-derived dendritic cells. Virol.,343 1 93 105 - 145.
Horscroft N Bellows D Ansari I Lai V. C Dempsey S Liang D Donis R andZhong W Hong Z 2005 Establishment of a sub genomic replicon for bovine viral diarrhoea virus in Huh-7 cells and modulation of interferon-regulated factor 3-mediated antiviral response. J. Virol.,79 2788 2796 - 146.
Carrasco C. P Rigden R. C Vincent I. E Balmelli C Ceppi M Bauhofer O Tache V Hjertner B Mcneilly F Van Gennip H. G andMccullough K. C Summerfield A 2004 Interaction of classical swine fever virus with dendritic cells. J. Gen. Virol.,85 1633 1641 - 147.
Ressang A. A 1973 Studies on the pathogenesis of hog cholera. II. Virus distribution in tissue and the morphology of the immune response. Zentbl. Vetmed. Reihe.,20 272 288 - 148.
Cella M Salio M Sakakibara Y Langen H Julkunen I Lanzavecchia A 1999 Maturation, activation, and protection of dendritic cells induced by double-stranded RNA. J. Exp. Med.,189 821 829 - 149.
Gomez-villamandos J. C Salguero F. J Ruiz-villamor E Sanchez-cordon P. J Bautista M. J Sierra M. A 2003 Classical swine fever: pathology of bone marrow. Vet. Pathol.,40 157 163 - 150.
Lackner T Muller A Pankraz A Becher P Thiel H. J andGorbalenya A. E Tautz N 2004 Temporal modulation of an autoprotease is crucial for replication and pathogenicity of an RNA virus. J. Virol.,78 10765 10775 - 151.
Iqbal M Poole E andGoodbourn S Mccauley J. W 2004 Role for bovine viral diarrhea virus Erns glycoprotein in the control of activation of beta interferon by double-stranded RNA. J. Virol.,78 136 145 - 152.
The Down-regulation of MHC molecule of monocytic cells after classical swine fever virus infection. Graudte Institute of Veterinary Pathology and Department of Veterinary Medicine, National Chung Hsing University, Taiwan, ROC.Wang C. S Chen S. C Yu N. J Chien M. S andLin C. C Lee W. C - 153.
Veterinary Virology, 3rd Edition.Murphy F. A Gibbs E. P. J andHorzinek M. C Studdert M. J - 154.
Susa M Konig M Saalmuller A andReddehase M. J Thiel H. J 1992 Pathogenesis of Classical Swine Fever: B-lymphocyte deficiency caused caused by Hog cholera virus. J. Virol.,66 2 1171 1175 - 155.
or not to B: that is the question. Immunol. Today. andGallagher R. B Osmond D. G 1991 To B 12 1 3 - 156.
Ehrensperger F 1989 Immunological aspects of the infection,143 163 In B. Liess (ed.), Classical swine fever and related viral infections. Martinus Nijhoff Publishing, Boston. - 157.
Van Oirschot J. T 1988 Description of the virus infection,1 25 In B. Liess (ed.), Classical swine fever and related viral infections. Martinus Nijhoff Publishing, Boston.