theilovirus

Summary

Summary: A species of CARDIOVIRUS which contains three strains: Theiler's murine encephalomyelitis virus, Vilyuisk human encephalomyelitis virus, and Rat encephalomyelitis virus.

Top Publications

  1. McDole J, Danzer S, Pun R, Chen Y, Johnson H, Pirko I, et al. Rapid formation of extended processes and engagement of Theiler's virus-infected neurons by CNS-infiltrating CD8 T cells. Am J Pathol. 2010;177:1823-33 pubmed publisher
  2. Jin Y, Kang B, Kim B. Theiler's virus infection induces a predominant pathogenic CD4+ T cell response to RNA polymerase in susceptible SJL/J mice. J Virol. 2009;83:10981-92 pubmed publisher
  3. Dethlefs S, Escriou N, Brahic M, Van Der Werf S, Larsson Sciard E. Theiler's virus and Mengo virus induce cross-reactive cytotoxic T lymphocytes restricted to the same immunodominant VP2 epitope in C57BL/6 mice. J Virol. 1997;71:5361-5 pubmed
    ..This epitope is immunodominant in C57BL/6 mice infected with Theiler's virus. The VP2(122-130) epitope, initially identified for Mengo virus, is the first CTL epitope described for Theiler's virus. ..
  4. Fiette L, Aubert C, Muller U, Huang S, Aguet M, Brahic M, et al. Theiler's virus infection of 129Sv mice that lack the interferon alpha/beta or interferon gamma receptors. J Exp Med. 1995;181:2069-76 pubmed
    ..They also lend support to the notion that the Ifg gene is involved in the resistance/susceptibility of inbred strains of mice to persistent infection by this picornavirus. ..
  5. Lyman M, Myoung J, Mohindru M, Kim B. Quantitative, not qualitative, differences in CD8(+) T cell responses to Theiler's murine encephalomyelitis virus between resistant C57BL/6 and susceptible SJL/J mice. Eur J Immunol. 2004;34:2730-9 pubmed
    ..These results suggest that an initial induction of a vigorous CD8(+) T cell response to TMEV is critically important for the resistance to virally induced demyelinating disease...
  6. Schulz O, Pichlmair A, Rehwinkel J, Rogers N, Scheuner D, Kato H, et al. Protein kinase R contributes to immunity against specific viruses by regulating interferon mRNA integrity. Cell Host Microbe. 2010;7:354-61 pubmed publisher
    ..Our results suggest that PKR plays a nonredundant role in IFN-alpha/beta production in response to some but not all viruses, in part by regulating IFN-alpha/beta mRNA stability...
  7. Lin X, Njenga M, Johnson A, Pavelko K, David C, Pease L, et al. Transgenic expression of Theiler's murine encephalomyelitis virus genes in H-2(b) mice inhibits resistance to virus-induced demyelination. J Virol. 2002;76:7799-811 pubmed
    ..Presented within the context of self-antigens, inactivation of these cells by ubiquitous expression of relevant virus capsid peptides partially inhibited resistance to virus-induced demyelination. ..
  8. Mestre L, Correa F, Arevalo Martin A, Molina Holgado E, Valenti M, Ortar G, et al. Pharmacological modulation of the endocannabinoid system in a viral model of multiple sclerosis. J Neurochem. 2005;92:1327-39 pubmed
    ..Taken together, these results point to the manipulation of the endocannabinoid system as a possible strategy to develop future MS therapeutic drugs. ..
  9. Lipton H, Kim B, Yahikozawa H, Nadler C. Serological evidence that Mus musculus is the natural host of Theiler's murine encephalomyelitis virus. Virus Res. 2001;76:79-86 pubmed
    ..These results indicate that Mus musculus is the natural host of TMEV. ..

More Information

Publications88

  1. Tsunoda I, Kuang L, Fujinami R. Induction of autoreactive CD8+ cytotoxic T cells during Theiler's murine encephalomyelitis virus infection: implications for autoimmunity. J Virol. 2002;76:12834-44 pubmed
    ..This is the first report demonstrating that TMEV can induce autoreactive cytotoxic cells that induce central nervous system pathology. ..
  2. Teuscher C, Rhein D, Livingstone K, Paynter R, Doerge R, Nicholson S, et al. Evidence that Tmevd2 and eae3 may represent either a common locus or members of a gene complex controlling susceptibility to immunologically mediated demyelination in mice. J Immunol. 1997;159:4930-4 pubmed
    ..9 and 37.2 cM, respectively. Taken together these results suggest that Tmevd2 and eae3 may represent either a single, common susceptibility gene or members of a gene complex involved in central nervous system immunopathology. ..
  3. Richards M, Getts M, Podojil J, Jin Y, Kim B, Miller S. Virus expanded regulatory T cells control disease severity in the Theiler's virus mouse model of MS. J Autoimmun. 2011;36:142-54 pubmed publisher
  4. Tsunoda I, Libbey J, Kobayashi Warren M, Fujinami R. IFN-gamma production and astrocyte recognition by autoreactive T cells induced by Theiler's virus infection: role of viral strains and capsid proteins. J Neuroimmunol. 2006;172:85-93 pubmed
    ..We hypothesized that, in DA virus infection, CD8+ CTLs specific for viral capsid protein could recognize self protein on oligodendrocytes by molecular mimicry, leading to demyelination. ..
  5. Lipton H, Kumar A, Trottier M. Theiler's virus persistence in the central nervous system of mice is associated with continuous viral replication and a difference in outcome of infection of infiltrating macrophages versus oligodendrocytes. Virus Res. 2005;111:214-23 pubmed
    ..Virus factors influencing persistence of TMEV are expression of the out-of-frame L* protein and use of sialic acid co-receptors...
  6. Myoung J, Bahk Y, Kang H, Dal Canto M, Kim B. Anticapsid immunity level, not viral persistence level, correlates with the progression of Theiler's virus-induced demyelinating disease in viral P1-transgenic mice. J Virol. 2008;82:5606-17 pubmed publisher
    ..These results strongly suggest that viral persistence alone is not sufficient to induce disease and that the level of T-cell immunity to viral capsid epitopes is critical for the development of demyelinating disease in SJL mice...
  7. Mohindru M, Kang B, Kim B. Initial capsid-specific CD4(+) T cell responses protect against Theiler's murine encephalomyelitisvirus-induced demyelinating disease. Eur J Immunol. 2006;36:2106-15 pubmed
  8. Tsunoda I, Kuang L, Kobayashi Warren M, Fujinami R. Central nervous system pathology caused by autoreactive CD8+ T-cell clones following virus infection. J Virol. 2005;79:14640-6 pubmed
    ..Intracerebral injection of the clones into naïve mice induced degeneration, not only in the brain, but also in the spinal cord. This suggests that CD8+ Tc1 cells could play a pathogenic role in central nervous system inflammation...
  9. Ortega Gutierrez S, Molina Holgado E, Arevalo Martin A, Correa F, Viso A, Lopez Rodriguez M, et al. Activation of the endocannabinoid system as therapeutic approach in a murine model of multiple sclerosis. FASEB J. 2005;19:1338-40 pubmed
    ..Overall, these results suggest that agents able to activate the endocannabinoid system could constitute a new series of drugs for the treatment of MS. ..
  10. Myoung J, Hou W, Kang B, Lyman M, Kang J, Kim B. The immunodominant CD8+ T cell epitope region of Theiler's virus in resistant C57BL/6 mice is critical for anti-viral immune responses, viral persistence, and binding to the host cells. Virology. 2007;360:159-71 pubmed
    ..Thus, selection of the cellular binding region of the virus as the predominant epitope for CD8+ T cells in resistant mice may provide a distinct advantage in controlling viral persistence by preventing escape mutations. ..
  11. Tsunoda I, Fujinami R. Inside-Out versus Outside-In models for virus induced demyelination: axonal damage triggering demyelination. Springer Semin Immunopathol. 2002;24:105-25 pubmed
    ..This implies that axonal injury could trigger demyelination. In this instance, lesions develop from the axon (inside) to the myelin (outside) (Inside-Out model). ..
  12. Himeda T, Okuwa T, Nojiri M, Muraki Y, Ohara Y. The anti-apoptotic protein L(*) of Theiler's murine encephalomyelitis virus (TMEV) contains a mitochondrial targeting signal. Virus Res. 2011;155:381-8 pubmed publisher
    ..These results suggest that the intra- or inter-molecular interaction of L(*) regulates its mitochondrial localization. It is also suggested that L(*) may inhibit the intrinsic apoptosis through the localization to mitochondria. ..
  13. Hause L, Al Salleeh F, Petro T. Expression of IL-27 p28 by Theiler's virus-infected macrophages depends on TLR3 and TLR7 activation of JNK-MAP-kinases. Antiviral Res. 2007;76:159-67 pubmed
    ..S macrophages. Therefore, macrophages expression of IL-27 p28 mRNA in response to TMEV is due to activation of TLR3, TLR7, and JNK MAPKs pathways. ..
  14. Drexler J, Baumgarte S, Luna L, Stocker A, Almeida P, Ribeiro T, et al. Genomic features and evolutionary constraints in Saffold-like cardioviruses. J Gen Virol. 2010;91:1418-27 pubmed publisher
    ..Accordingly, the results of this study suggest that SLCV and TMEV may represent distinct species within the genus Cardiovirus. ..
  15. Roussarie J, Ruffie C, Brahic M. The role of myelin in Theiler's virus persistence in the central nervous system. PLoS Pathog. 2007;3:e23 pubmed
    ..These results uncover an unsuspected axon to myelin traffic of Theiler's virus and the essential role played by the infection of myelin/oligodendrocyte in persistence...
  16. van Eyll O, Michiels T. Non-AUG-initiated internal translation of the L* protein of Theiler's virus and importance of this protein for viral persistence. J Virol. 2002;76:10665-73 pubmed
    ..The expression of the 18-kDa form is required for efficient persistence of DA virus derivatives in the central nervous system. ..
  17. Kang B, Lyman M, Kim B. The majority of infiltrating CD8+ T cells in the central nervous system of susceptible SJL/J mice infected with Theiler's virus are virus specific and fully functional. J Virol. 2002;76:6577-85 pubmed
    ..Interestingly, T-cell responses to all three epitopes are restricted by the H-2K(s) molecule, and this skewed class I restriction may be associated with susceptibility to demyelinating disease...
  18. So E, Kim B. Theiler's virus infection induces TLR3-dependent upregulation of TLR2 critical for proinflammatory cytokine production. Glia. 2009;57:1216-26 pubmed publisher
    ..These results indicate that TMEV utilizes TLR3-induced TLR2 to induce inflammatory cytokines, which are critical to the development of immune-mediated demyelinating disease...
  19. Buenz E, Rodriguez M, Howe C. Disrupted spatial memory is a consequence of picornavirus infection. Neurobiol Dis. 2006;24:266-73 pubmed
    ..An important implication of such subclinical virus-induced neurologic deficit is that the injury may accumulate over the lifetime of the individual, eventually leading to the manifestation of clinical cognitive or memory deficits...
  20. Olson J, Miller S. The innate immune response affects the development of the autoimmune response in Theiler's virus-induced demyelinating disease. J Immunol. 2009;182:5712-22 pubmed publisher
    ..These results demonstrate that activating or enhancing the innate immune response can reduce the subsequent initiation and progression of the autoimmune response and demyelinating disease...
  21. Mack C, Vanderlugt Castaneda C, Neville K, Miller S. Microglia are activated to become competent antigen presenting and effector cells in the inflammatory environment of the Theiler's virus model of multiple sclerosis. J Neuroimmunol. 2003;144:68-79 pubmed
  22. Palma J, Lee H, Mohindru M, Kang B, Dal Canto M, Miller S, et al. Enhanced susceptibility to Theiler's virus-induced demyelinating disease in perforin-deficient mice. J Neuroimmunol. 2001;116:125-35 pubmed
    ..In addition, immunization of pKO mice with UV-inactivated virus further enhanced clinical incidence and accelerated the disease course. Thus, perforin is most likely involved in viral clearance, hence protection from the disease. ..
  23. Correa F, Hernangómez Herrero M, Mestre L, Loría F, Docagne F, Guaza C. The endocannabinoid anandamide downregulates IL-23 and IL-12 subunits in a viral model of multiple sclerosis: evidence for a cross-talk between IL-12p70/IL-23 axis and IL-10 in microglial cells. Brain Behav Immun. 2011;25:736-49 pubmed publisher
    ..Accordingly, pharmacological modulation of endocannabinoids might be a useful tool for treating neuroinflammatory diseases. ..
  24. Murray P, Pavelko K, Leibowitz J, Lin X, Rodriguez M. CD4(+) and CD8(+) T cells make discrete contributions to demyelination and neurologic disease in a viral model of multiple sclerosis. J Virol. 1998;72:7320-9 pubmed
  25. Sun G, Zhang X, Yi M, Shao S, Zhang W. Analysis of the genomic homologous recombination in Theilovirus based on complete genomes. Virol J. 2011;8:439 pubmed publisher
    At present, Theilovirus is considered to comprise four distinct serotypes, including Theiler's murine encephalomyelitis virus, Vilyuisk human encephalomyelitis virus, Thera virus, and Saffold virus...
  26. Carpentier P, Getts M, Miller S. Pro-inflammatory functions of astrocytes correlate with viral clearance and strain-dependent protection from TMEV-induced demyelinating disease. Virology. 2008;375:24-36 pubmed publisher
    ..These results suggest that enhanced anti-viral responses of B6 astrocytes contribute to the ability of these mice to clear TMEV from the CNS and therefore to their resistance to the development of autoimmune demyelinating disease. ..
  27. Bihl F, Pena Rossi C, Guenet J, Brahic M, Bureau J. The shiverer mutation affects the persistence of Theiler's virus in the central nervous system. J Virol. 1997;71:5025-30 pubmed
    ..These results strongly support the view that oligodendrocytes are a necessary viral target for the establishment of a persistent infection by Theiler's virus...
  28. So E, Kang M, Kim B. Induction of chemokine and cytokine genes in astrocytes following infection with Theiler's murine encephalomyelitis virus is mediated by the Toll-like receptor 3. Glia. 2006;53:858-67 pubmed
  29. Kang H, Kim B. Predominant clonal accumulation of CD8+ T cells with moderate avidity in the central nervous systems of Theiler's virus-infected C57BL/6 mice. J Virol. 2010;84:2774-86 pubmed publisher
    ..Therefore, our findings provide new insights into the CD8(+) T-cell repertoire during immune responses to viral infection in the CNS. ..
  30. Kang B, Kang H, Kim B. Identification of capsid epitopes of Theiler's virus recognized by CNS-infiltrating CD4+ T cells from virus-infected C57BL/6 mice. Virus Res. 2005;108:57-61 pubmed
    ..Therefore, these newly defined CD4+ T cell epitopes are likely to provide an important tool to investigate the role of CD4+ T cell responses in H-2b-bearing congenic strains. ..
  31. Tsunoda I, Kuang L, Libbey J, Fujinami R. Axonal injury heralds virus-induced demyelination. Am J Pathol. 2003;162:1259-69 pubmed
    ..The distribution of axonal injury observed during the early phase corresponded to regions where subsequent demyelination occurs during the chronic phase. The results suggest that axonal injury might herald or trigger demyelination. ..
  32. Miller S, Olson J, Croxford J. Multiple pathways to induction of virus-induced autoimmune demyelination: lessons from Theiler's virus infection. J Autoimmun. 2001;16:219-27 pubmed
  33. Jnaoui K, Minet M, Michiels T. Mutations that affect the tropism of DA and GDVII strains of Theiler's virus in vitro influence sialic acid binding and pathogenicity. J Virol. 2002;76:8138-47 pubmed
    ..Mutations affecting tropism in vitro and sialic acid binding dramatically affected the persistence and neurovirulence of the viruses. ..
  34. Kumar A, Kallio P, Luo M, Lipton H. Amino acid substitutions in VP2 residues contacting sialic acid in low-neurovirulence BeAn virus dramatically reduce viral binding and spread of infection. J Virol. 2003;77:2709-16 pubmed
    ..In addition, a gain of function-revertant virus was recovered with the Q2161A mutation after prolonged passage in cells. ..
  35. Njenga M, Coenen M, DeCuir N, Yeh H, Rodriguez M. Short-term treatment with interferon-alpha/beta promotes remyelination, whereas long-term treatment aggravates demyelination in a murine model of multiple sclerosis. J Neurosci Res. 2000;59:661-70 pubmed
    ..These results indicate that the length of type I IFN treatment may have paradoxical effects on demyelination and remyelination...
  36. Mestre L, Correa F, Docagne F, Clemente D, Guaza C. The synthetic cannabinoid WIN 55,212-2 increases COX-2 expression and PGE2 release in murine brain-derived endothelial cells following Theiler's virus infection. Biochem Pharmacol. 2006;72:869-80 pubmed
    ..Overexpression of COX-2 and the subsequent increase of PGE2 could be affecting flow blood and/or immune reactivity. ..
  37. Azoulay Cayla A, Dethlefs S, Perarnau B, Larsson Sciard E, Lemonnier F, Brahic M, et al. H-2D(b-/-) mice are susceptible to persistent infection by Theiler's virus. J Virol. 2000;74:5470-6 pubmed
    ..These results demonstrate that the H-2D(b) and H-2K(b) genes play nonredundant roles in the resistance to this persistent infection. ..
  38. Schlitt B, Felrice M, Jelachich M, Lipton H. Apoptotic cells, including macrophages, are prominent in Theiler's virus-induced inflammatory, demyelinating lesions. J Virol. 2003;77:4383-8 pubmed
    ..T cells comprised 74% of apoptotic cells, while 8% were macrophages, 0.6% were astrocytes, and approximately 17% remained unidentified. In situ hybridization revealed viral RNA in approximately 1% of apoptotic cells. ..
  39. van Pesch V, van Eyll O, Michiels T. The leader protein of Theiler's virus inhibits immediate-early alpha/beta interferon production. J Virol. 2001;75:7811-7 pubmed
    ..In agreement with the anti-interferon role of the L protein, a virus bearing a mutation in the zinc-binding motif was dramatically impaired in its ability to persist in the central nervous system of SJL/J mice...
  40. Lipton H, Kumar A, Hertzler S, Reddi H. Differential usage of carbohydrate co-receptors influences cellular tropism of Theiler's murine encephalomyelitis virus infection of the central nervous system. Glycoconj J. 2006;23:39-49 pubmed
  41. Reddi H, Kallio P, Lipton H. Galactose is needed only for expression of co-receptors used by Theiler's murine encephalomyelitis virus as the virus does not directly bind galactose or use the UDP-galactose transporter as a receptor. J Gen Virol. 2003;84:845-9 pubmed
    ..Excluding direct involvement of UGT and galactose in TMEV binding and entry provides further insight into how TMEV interacts with the host cell and should facilitate ongoing studies to identify a TMEV receptor. ..
  42. Butterfield R, Roper R, Rhein D, Melvold R, Haynes L, Ma R, et al. Sex-specific quantitative trait loci govern susceptibility to Theiler's murine encephalomyelitis virus-induced demyelination. Genetics. 2003;163:1041-6 pubmed
    ..Our results support the existence of three linked sex-specific QTL on chromosome 1 with opposing effects on the severity of the clinical signs of TMEV-induced disease in male and female mice...
  43. Steurbaut S, Rombaut B, Vrijsen R. Persistent infection of RAW264.7 macrophages with the DA strain of Theiler's murine encephalomyelitis virus: An in vitro model to study viral persistence. J Neurovirol. 2006;12:108-15 pubmed
    ..This persistently DA-infected macrophage cell line, which we have called DRAW, provides a model to investigate the interactions between the cellular and viral factors influencing persistence and to screen for anti-TMEV agents...
  44. Kirkman N, Libbey J, Wilcox K, White H, Fujinami R. Innate but not adaptive immune responses contribute to behavioral seizures following viral infection. Epilepsia. 2010;51:454-64 pubmed publisher
    ..This model is a potential infection-driven model of mesial temporal lobe epilepsy with hippocampal sclerosis. ..
  45. Jin Y, Hou W, Kim S, Fuller A, Kang B, Goings G, et al. Type I interferon signals control Theiler's virus infection site, cellular infiltration and T cell stimulation in the CNS. J Neuroimmunol. 2010;226:27-37 pubmed publisher
    ..These results suggest that IFN-I-mediated signals play important roles in controlling cellular infiltration to the CNS and shaping local T cell immune responses...
  46. Fuller K, Olson J, Howard L, Croxford J, Miller S. Mouse models of multiple sclerosis: experimental autoimmune encephalomyelitis and Theiler's virus-induced demyelinating disease. Methods Mol Med. 2004;102:339-61 pubmed
    ..Recombinant TMEV strains have been created for the study of molecular mimicry; these strains incorporate 30 various amino acid myelin epitopes within the leader region of TMEV...
  47. Aubagnac S, Brahic M, Bureau J. Viral load and a locus on chromosome 11 affect the late clinical disease caused by Theiler's virus. J Virol. 1999;73:7965-71 pubmed
    ..Clinical disease depends on high viral load and Tmevd5, a locus on chromosome 11. These results have consequences for the identification of viruses which might be implicated in multiple sclerosis...
  48. Petro T. ERK-MAP-kinases differentially regulate expression of IL-23 p19 compared with p40 and IFN-beta in Theiler's virus-infected RAW264.7 cells. Immunol Lett. 2005;97:47-53 pubmed
    ..Interestingly, U0126 prolonged TMEV-induced ATF-2 activation to at least 3h. Thus ERK MAPKs regulate expression of TMEV-induced p19 differently than p40 and IFN-beta suggesting the benefits of U0126 in treatment of DD. ..
  49. Deb C, Howe C. NKG2D contributes to efficient clearance of picornavirus from the acutely infected murine brain. J Neurovirol. 2008;14:261-6 pubmed publisher
  50. Stewart K, Wilcox K, Fujinami R, White H. Development of postinfection epilepsy after Theiler's virus infection of C57BL/6 mice. J Neuropathol Exp Neurol. 2010;69:1210-9 pubmed publisher
    ..Importantly, this model will also be useful to investigate novel therapies for the treatment and prevention of epilepsy. ..
  51. Son K, Becker R, Kallio P, Lipton H. Theiler's virus-induced intrinsic apoptosis in M1-D macrophages is Bax mediated and restricts virus infectivity: a mechanism for persistence of a cytolytic virus. J Virol. 2008;82:4502-10 pubmed publisher
    ..Thus, BeAn virus infection in M1-D macrophages, which restricts virus replication, provides a potential mechanism for modulating TMEV neurovirulence during persistence in the mouse central nervous system. ..
  52. McMahon E, Bailey S, Castenada C, Waldner H, Miller S. Epitope spreading initiates in the CNS in two mouse models of multiple sclerosis. Nat Med. 2005;11:335-9 pubmed
    ..The data suggest that naive T cells enter the inflamed CNS and are activated by local APCs, possibly DCs, to initiate epitope spreading. ..
  53. Himeda T, Ohara Y, Asakura K, Kontani Y, Sawada M. A lentiviral expression system demonstrates that L* protein of Theiler's murine encephalomyelitis virus (TMEV) has an anti-apoptotic effect in a macrophage cell line. Microb Pathog. 2005;38:201-7 pubmed
    ..Therefore, we established P388D1 cells that continuatively express L*, in order to confirm its role in TMEV-induced apoptosis. The anti-apoptotic activity of L* may be important in TMEV pathogenesis. ..
  54. Fuller A, Kang B, Kang H, Yahikozowa H, Dal Canto M, Kim B. Gender bias in Theiler's virus-induced demyelinating disease correlates with the level of antiviral immune responses. J Immunol. 2005;175:3955-63 pubmed
    ..Male mice in contrast do not mount as effective an immune response, thereby allowing for eventual viral persistence in the CNS and continuous T cell expansion leading to clinical symptoms. ..
  55. Brahic M, Bureau J, Michiels T. The genetics of the persistent infection and demyelinating disease caused by Theiler's virus. Annu Rev Microbiol. 2005;59:279-98 pubmed
    ..H2 class I genes have a major effect on susceptibility. Among several non-H2 susceptibility loci, Tmevp3 appears to regulate the expression of important cytokines...
  56. Brahic M. Theiler's virus infection of the mouse, or: of the importance of studying animal models. Virology. 2002;301:1-5 pubmed
  57. Olson J, Miller S. Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs. J Immunol. 2004;173:3916-24 pubmed
    ..Thus, microglia appear to be a unique and important component of both the innate and adaptive immune response, providing the CNS with a means to rapidly and efficiently respond to a wide variety of pathogens. ..
  58. Bowen J, Olson J. Innate immune CD11b+Gr-1+ cells, suppressor cells, affect the immune response during Theiler's virus-induced demyelinating disease. J Immunol. 2009;183:6971-80 pubmed publisher
  59. McClelland E, Penn D, Potts W. Major histocompatibility complex heterozygote superiority during coinfection. Infect Immun. 2003;71:2079-86 pubmed
  60. Buenz E, Sauer B, Lafrance Corey R, Deb C, Denic A, German C, et al. Apoptosis of hippocampal pyramidal neurons is virus independent in a mouse model of acute neurovirulent picornavirus infection. Am J Pathol. 2009;175:668-84 pubmed publisher
    ..These observations suggest that therapeutic strategies other than antiviral interventions may be useful for neuroprotection during acute CNS picornavirus infection. ..
  61. Hou W, Kang H, Kim B. Th17 cells enhance viral persistence and inhibit T cell cytotoxicity in a model of chronic virus infection. J Exp Med. 2009;206:313-28 pubmed publisher
    ..Thus, these results indicate a novel pathogenic role of Th17 cells via IL-17 in persistent viral infection and its associated chronic inflammatory diseases...
  62. Jelachich M, Bramlage C, Lipton H. Differentiation of M1 myeloid precursor cells into macrophages results in binding and infection by Theiler's murine encephalomyelitis virus and apoptosis. J Virol. 1999;73:3227-35 pubmed
    ..These data suggest that macrophage differentiation plays a role in susceptibility to TMEV infection and apoptosis...
  63. Turrin N. Central nervous system Toll-like receptor expression in response to Theiler's murine encephalomyelitis virus-induced demyelination disease in resistant and susceptible mouse strains. Virol J. 2008;5:154 pubmed publisher
    ..This could have implications on therapies that target TLRs to prevent the emergence of conditions such as MS in patients at risk for the disease. ..
  64. Loría F, Petrosino S, Mestre L, Spagnolo A, Correa F, Hernangómez M, et al. Study of the regulation of the endocannabinoid system in a virus model of multiple sclerosis reveals a therapeutic effect of palmitoylethanolamide. Eur J Neurosci. 2008;28:633-41 pubmed publisher
    ..This study overall highlights the potential therapeutic effects of endocannabinoids in MS. ..
  65. Pirko I, Gamez J, Johnson A, Macura S, Rodriguez M. Dynamics of MRI lesion development in an animal model of viral-induced acute progressive CNS demyelination. Neuroimage. 2004;21:576-82 pubmed
    ..These novel findings may provide new insights into the pathogenesis of acute fulminant multiple sclerosis (MS)...
  66. Pavelko K, Girtman M, Mitsunaga Y, Mendez Fernandez Y, Bell M, Hansen M, et al. Theiler's murine encephalomyelitis virus as a vaccine candidate for immunotherapy. PLoS ONE. 2011;6:e20217 pubmed publisher
    ..We propose that epitope-modified TMEV is an excellent candidate for further development as a human T-cell vaccine for use in immunotherapy. ..
  67. Arevalo Martin A, Vela J, Molina Holgado E, Borrell J, Guaza C. Therapeutic action of cannabinoids in a murine model of multiple sclerosis. J Neurosci. 2003;23:2511-6 pubmed
  68. Karpus W, Kennedy K, Fife B, Bennett J, Dal Canto M, Kunkel S, et al. Anti-CCL2 treatment inhibits Theiler's murine encephalomyelitis virus-induced demyelinating disease. J Neurovirol. 2006;12:251-61 pubmed
    ..Finally, anti-CCL2 treatment resulted in decreased viral load in the CNS. These data directly demonstrate a role for CCL2 in the pathogenesis of TMEV-IDD...
  69. Palma J, Kim B. The scope and activation mechanisms of chemokine gene expression in primary astrocytes following infection with Theiler's virus. J Neuroimmunol. 2004;149:121-9 pubmed
  70. Trottier M, Schlitt B, Kung A, Lipton H. Transition from acute to persistent Theiler's virus infection requires active viral replication that drives proinflammatory cytokine expression and chronic demyelinating disease. J Virol. 2004;78:12480-8 pubmed
    ..i. and that active viral replication with high viral genome loads leads to increased levels of Th1 cytokines that drive disease progression in infected mice...
  71. Mendez Fernandez Y, Hansen M, Rodriguez M, Pease L. Anatomical and cellular requirements for the activation and migration of virus-specific CD8+ T cells to the brain during Theiler's virus infection. J Virol. 2005;79:3063-70 pubmed
  72. Monteyne P, Bureau J, Brahic M. The infection of mouse by Theiler's virus: from genetics to immunology. Immunol Rev. 1997;159:163-76 pubmed
    ..CD4+ T cells participate both in protection against the infection and in demyelination. Finally, the effect of non-immune factors in resistance is illustrated by mice with mutations in the MBP or PLP gene. ..
  73. Howe C, Lafrance Corey R, Sundsbak R, Lafrance S. Inflammatory monocytes damage the hippocampus during acute picornavirus infection of the brain. J Neuroinflammation. 2012;9:50 pubmed publisher
    ..These effector cells may be important therapeutic targets for immunomodulatory or immunosuppressive therapies aimed at reducing or preventing central nervous system pathology associated with acute viral infection. ..
  74. Delhaye S, van Pesch V, Michiels T. The leader protein of Theiler's virus interferes with nucleocytoplasmic trafficking of cellular proteins. J Virol. 2004;78:4357-62 pubmed
    ..The leader protein also interfered with trafficking of the cytoplasmic interferon regulatory factor 3, a factor critical for transcriptional activation of alpha/beta interferon genes. ..
  75. Olson J, Eagar T, Miller S. Functional activation of myelin-specific T cells by virus-induced molecular mimicry. J Immunol. 2002;169:2719-26 pubmed
    ..Collectively, infection with PLP139-151 mimic encoding TMEV serves as an excellent model for molecular mimicry by inducing pathologic myelin-specific CD4(+) T cells via a natural virus infection. ..
  76. Martinat C, Mena I, Brahic M. Theiler's virus infection of primary cultures of bone marrow-derived monocytes/macrophages. J Virol. 2002;76:12823-33 pubmed
    ..The role of alpha/beta interferon was confirmed by the observation that monocytes/macrophages from IFNA/BR(-/-) mice were fully permissive. ..
  77. Kim B, Palma J, Kwon D, Fuller A. Innate immune response induced by Theiler's murine encephalomyelitis virus infection. Immunol Res. 2005;31:1-12 pubmed
    ..In this review, the type of cells and molecules, gene-activation mechanisms as well as their potential roles in protection and pathogenesis will be discussed. ..
  78. Levillayer F, Mas M, Levi Acobas F, Brahic M, Bureau J. Interleukin 22 is a candidate gene for Tmevp3, a locus controlling Theiler's virus-induced neurological diseases. Genetics. 2007;176:1835-44 pubmed
    ..Il22, a member of the IL-10 cytokine family, is a candidate gene for the control of mortality during the acute encephalomyelitis. ..
  79. Rodriguez M, Zoecklein L, Howe C, Pavelko K, Gamez J, Nakane S, et al. Gamma interferon is critical for neuronal viral clearance and protection in a susceptible mouse strain following early intracranial Theiler's murine encephalomyelitis virus infection. J Virol. 2003;77:12252-65 pubmed
    ..These data support the hypothesis that IFN-gamma plays a critical role in protecting spinal cord neurons from persistent infection and death...