Disease relevance of Theilovirus

• The effect of immunosuppression with cyclophosphamide and rabbit antiserum to mouse thymocytes on demyelination induced by Theiler's virus in SJL/J mice was ascertained from Epon-embedded sections (1 micrometer) of the central nervous system [1].
• In this study we demonstrate perforin-mediated cytotoxic effector function is necessary for viral clearance and may directly contribute to the development of neurologic deficits after demyelination in the Theiler's murine encephalomyelitis virus (TMEV) model of multiple sclerosis [2].
• To determine the potential of virus-induced autoimmunity by molecular mimicry, a nonpathogenic neurotropic Theiler's murine encephalomyelitis virus variant was engineered to encode a mimic peptide from protease IV of Haemophilus influenzae (HI), sharing 6 of 13 aa with the dominant encephalitogenic proteolipid protein (PLP) epitope PLP(139-151) [3].
• To determine the potential activity of MSP in CNS demyelination, we examined its expression in multiple sclerosis lesions and in two animal models of multiple sclerosis: Theiler's murine encephalomyelitis virus (TMEV) and myelin oligodendrocyte glycoprotein (MOG)-induced experimental allergic encephalomyelitis (EAE) in marmosets [4].
• The third gene codes for a new IFN-alpha subtype called IFN-alpha13, which exhibits acid-stable antiviral activity against Theiler's virus, Mengo virus, and vesicular stomatitis virus [5].

High impact information on Theilovirus

• Theiler's virus infection of 129Sv mice that lack the interferon alpha/beta or interferon gamma receptors [6].
• Furthermore, a competition ELISA for TMEV or GC antigen revealed that sera from these infected mice contained antibody(s) with the same specificity as mAb H8 [7].
• The IRES of a neurovirulent picornavirus, the GDVII strain of Theiler's murine encephalomyelitis virus, requires polypyrimidine tract-binding protein (PTB) for its function [8].
• Hematopoietic transplant performed after onset of disease resulted in 42% mortality in SJL/J syngeneic transplants, 47% mortality in diseased DBA2 recipients restored with marrow from naive B6D2 donors, and 12% in diseased DBA2 recipients receiving marrow from B6D2 donors previously infected with TMEV [9].
• CD40L-mediated interactions were also necessary for development of protective H-2b-restricted cytotoxic T cell responses directed against the VP2 region of TMEV as well as for spontaneous remyelination of the spinal cord white matter [10].

Chemical compound and disease context of Theilovirus

• Treatment of SJL/J mice with TMEV-coupled, ethyl carbodiimide-treated splenocytes either before or after infection with live TMEV prevented the development of clinical disease, including inflammation and demyelination in the CNS [11].
• A naturally occurring, low pathogenic Theiler's murine encephalomyelitis virus variant showed a single amino acid change within a predominant Th epitope from lysine to arginine at position 244 of VP1 [12].
• Virus binding was also blocked by wheat germ agglutinin, which specifically binds to sialic acid residues and blocks TMEV binding to whole BHK-21 cells [13].
• Thus, we demonstrated that the single nucleotide change resulting in an amino acid substitution at position 101 (threonine to isoleucine) of VP-1 determines one aspect of Theiler's virus persistence and disease in mice [14].
• We report the effect of sialylation on cell surface on entry and the complex structure of DA virus, a persistent TMEV, and the receptor moiety mimic, sialyllactose, refined to a resolution of 3.0 A [15].

Biological context of Theilovirus

• IFN-gamma(-/-) and IFN-gamma(+/+) mice of the resistant major histocompatibility complex (MHC) H-2(b) haplotype and intracerebrally infected with Theiler's murine encephalomyelitis virus (TMEV) cleared virus infection from anterior horn cell neurons [16].
• To provide information about the TMEV classification, genome organization, and protein processing map, we determined the complete nucleotide sequence of the TMEV genome and deduced the amino acid sequence of the polyprotein coding region [17].
• Resistance to persistent TMEV infection maps to he D locus of the major histocompatibility complex suggesting a prominent role of antiviral CTL in the protective immune response [18].
• To investigate the mechanisms of such inflammatory diseases, potential chemokine gene activation in human astrocytes was investigated following infection with Theiler's murine encephalomyelitis virus (TMEV), coxsackievirus B3 (CVB3), or coxsackievirus B4 (CVB4) [19].
• The scope and activation mechanisms of chemokine gene expression in primary astrocytes following infection with Theiler's virus [20].

Anatomical context of Theilovirus

• When resistant (C57BL/10) mice were depleted of NK cells using either mAb NK1.1 or polyclonal anti-asialo-GM1, TMEV induced the development of diffuse encephalitis and meningitis early in the postinfection period (days 6 to 11) [21].
• Infection with Theiler's murine encephalomyelitis virus directly induces proinflammatory cytokines in primary astrocytes via NF-kappaB activation: potential role for the initiation of demyelinating disease [22].
• Split tolerance of Th1 and Th2 cells in tolerance to Theiler's murine encephalomyelitis virus [23].
• Treatment with 80 mg kg(-1) day(-1) of Linomide beginning at the time of infection significantly increased the number of Theiler's murine encephalomyelitis virus (TMEV)-positive cells mm(-2) of spinal cord white matter [24].
• Macrophages infected with TMEV increased IL-12p40 production and activation of CB2 receptors by JWH-133 (100 nM) inhibited it [25].

Gene context of Theilovirus

• Tmevpg1, a candidate gene for the control of Theiler's virus persistence, could be implicated in the regulation of gamma interferon [26].
• The Tmevp3 locus controls the load of Theiler's virus RNA during persistent infection of the mouse central nervous system (CNS) [26].
• In this study, we investigated whether the NF-kappaB-dependent inflammatory responses after TMEV infection is triggered through TLR3 and/or TLR7 [27].
• Indeed, IL-4 or IL-10 up-regulated IkappaBalpha mRNA levels after TMEV infection [28].
• Membrane lymphotoxin is required for resistance to Theiler's virus infection [29].

Analytical, diagnostic and therapeutic context of Theilovirus

• Intraperitoneal injection of LPS, concomitant with intracerebral of genetically resistant C57BL/6 mice with TMEV, resulted in clinical symptoms in approximately 50% of the group [30].
• In the experimental model using Theiler's murine encephalomyelitis virus, competition radioimmunoassay failed to detect any cross-reaction between MBP and VP1, VP2 and VP3 envelope antigens [31].

References