Antigens to viral capsid and non-capsid proteins are present in brain tissues and antibodies in sera of Theiler's virus-infected mice

Cameron, Kjerstin T.; Zhang, Xuexian; Seal, Bruce S.; Rodriguez, Moses; Njenga, M. Kariuki

doi:10.1016/s0166-0934(00)00246-9

Cited by 7 publications

(7 citation statements)

References 25 publications

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“…Mice expressing the 3D transgene were used as control mice, since previous studies have shown that the 3D protein was ignored by T and B cells in the immune system (3,22,29). To our surprise, we found that the 3D transgenic mice substantially reduced TMEV in vivo.…”

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confidence: 64%

Transgenic Expression of the 3D Polymerase Inhibits Theiler's Virus Infection and Demyelination

Kerkvliet¹,

Zoecklein²,

Papke³

et al. 2009

J Virol

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The RNA-dependent RNA polymerase 3D pol is required for the elongation of positive-and negative-stranded picornavirus RNA. During the course of investigating the effect of the transgenic expression of viral genes on the host immune response, we evaluated the viral load present in the host after infection. To our surprise, we found that 3D transgenic expression in genetically susceptible FVB mice led to substantially lower viral loads after infection with Theiler's murine encephalomyelitis virus (TMEV). As a result, spinal cord damage caused by chronic viral infection in the central nervous system was reduced in FVB mice that expressed 3D. This led to the preservation of large-diameter axons and motor function in these mice. The 3D transgene also lowered early viral loads when expressed in FVB-D b mice resistant to persistent TMEV infection. The protective effect of 3D transgenic expression was not altered in FVB-Rag ؊/؊ .3D mice that are deficient in T and B cells, thus ruling out a mechanism by which the overexpression of 3D enhanced the adaptive immune clearance of the virus. Understanding how endogenously overexpressed 3D polymerase inhibits viral replication may lead to new strategies for targeting therapies to all picornaviruses.

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mentioning

confidence: 64%

Transgenic Expression of the 3D Polymerase Inhibits Theiler's Virus Infection and Demyelination

Kerkvliet¹,

Zoecklein²,

Papke³

et al. 2009

J Virol

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“…Varrasso et al, (2001) identified neutralisation sites located within the N and C termini as well as the βE-βF and βG-βH loops of Equine Rhinitis Virus (ERAV) VP1, with strong antibody recognition against the N-terminus. Similarly, major VP1 neutralisation sites have been reported for TMEV (Cameron et al, 2001;Luo et al, 1992) and the enteroviruses (Mateu, 1995;Oberste et al, 1999;Wu et al, 2001) with key neutralising determinants located in the N-terminal region of VP1 (Bobek et al, 2010;Tan and Cardosa, 2007) .…”

Section: Introductionmentioning

confidence: 62%

Subcellular localisation of Theiler's murine encephalomyelitis virus (TMEV) capsid subunit VP1 vis-á-vis host protein Hsp90

et al. 2016

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Highlights TMEV VP1 localises to the perinuclear region and cytoplasm of infected cells  TMEV VP1 and Hsp90 colocalise in the perinuclear region and cytoplasm  TMEV VP1 did not localise to the nucleus during infection  A typical NLS was absent from the TMEV VP1 sequence  TMEV VP1 localises in a similar manner to FMDV and EV71 VP1 AbstractThe VP1 subunit of the picornavirus capsid is the major antigenic determinant and mediates host cell attachment and virus entry. To investigate the localisation of Theiler's murine encephalomyelitis virus (TMEV) VP1 during infection, a bioinformatics approach was used to predict a surface-exposed, linear epitope region of the protein for subsequent expression and purification. This region, comprising the N-terminal 112 amino acids of the protein, was then used for rabbit immunisation, and the resultant polyclonal antibodies were able to recognise full length VP1 in infected cell lysates by Western blot. Following optimisation, the antibodies were used to investigate the localisation of VP1 in relation to Hsp90 in infected cells by indirect immunofluorescence and confocal microscopy. At 5 hours post infection, VP1 was distributed diffusely in the cytoplasm with strong perinuclear staining but was absent from the nucleus of all cells analysed. Dual-label immunofluorescence using anti-TMEV VP1 and anti-Hsp90 antibodies indicated that the distribution of both proteins colocalised in the cytoplasm and perinuclear region of infected cells. This is the first report describing the localisation of TMEV VP1 in infected cells, and the antibodies produced provide a valuable tool for investigating the poorly understood mechanisms underlying the early steps of picornavirus assembly.

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“…Thus, it would not be unreasonable for antibodies against VP4 to also be produced in TMEV infection, leading to virus neutralization. In fact, sera from SJL/J mice infected with TMEV were shown to react with the VP4 protein (Cameron et al 2001). …”

Section: Discussionmentioning

confidence: 99%

Immunization with structural and non-structural proteins of Theiler’s murine encephalomyelitis virus alters demyelinating disease

2012

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Theiler’s murine encephalomyelitis virus (TMEV) causes a demyelinating disease similar to multiple sclerosis in the central nervous system (CNS) of susceptible SJL/J mice. Immune responses to TMEV contribute to viral clearance as well as to demyelination. We constructed recombinant vaccinia viruses (VV) that encode each or all of the capsid proteins (VVVP1, VVVP2, VVVP3, VVVP4, and VVall) or non-structural proteins (VVP2, VVP2P3, and VV3′P3) of the Daniels strain of TMEV. To determine the role of each of the coding regions of TMEV in vivo, we immunized SJL/J mice with each recombinant VV, with or without subsequent TMEV infection. The groups of mice were compared clinically, immunologically, and histologically. No mice immunized with any recombinant VV without subsequent TMEV infection developed demyelination. However, antibody responses to TMEV were detected in mice immunized with VVall. In addition, in some mice, VVP2 immunization induced mild meningitis. VVVP3 or VVVP4 immunization of mice prior to TMEV infection ameliorated TMEV-induced pathology or clinical signs of disease. The beneficial effect of VP4 immunization was also seen through DNA immunization with a plasmid encoding VP4 and leader prior to TMEV infection. Therefore, vaccination against not only surface capsid proteins (VVVP3 and VVall) but also non-surface capsid protein (VVVP4), and non-structural proteins (VVP2) can elicit immune responses to virus or modulate subsequent viral-induced CNS disease.

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Antigens to viral capsid and non-capsid proteins are present in brain tissues and antibodies in sera of Theiler's virus-infected mice

Cited by 7 publications

References 25 publications

Transgenic Expression of the 3D Polymerase Inhibits Theiler's Virus Infection and Demyelination

Transgenic Expression of the 3D Polymerase Inhibits Theiler's Virus Infection and Demyelination

Subcellular localisation of Theiler's murine encephalomyelitis virus (TMEV) capsid subunit VP1 vis-á-vis host protein Hsp90

Immunization with structural and non-structural proteins of Theiler’s murine encephalomyelitis virus alters demyelinating disease

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