CMV infection attenuates the disease course in a murine model of multiple sclerosis

Istvan Pirko, Rhonda Cardin, Yi Chen, Anne K. Lohrey, Diana M. Lindquist, R. Scott Dunn, Robert Zivadinov, Aaron J. Johnson

Research output: Contribution to journalArticle

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Abstract

Recent evidence in multiple sclerosis (MS) suggests that active CMV infection may result in more benign clinical disease. The goal of this pilot study was to determine whether underlying murine CMV (MCMV) infection affects the course of the Theiler's murine encephalitis virus (TMEV) induced murine model of MS. A group of eight TMEV-infected mice were co-infected with MCMV at 2 weeks prior to TMEV infection while a second group of TMEV-infected mice received MCMV two weeks post TMEV. We also used 2 control groups, where at the above time points MCMV was replaced with PBS. Outcome measures included (1) monthly monitoring of disability via rotarod for 8 months; (2) in vivo MRI for brain atrophy studies and (3) FACS analysis of brain infiltrating lymphocytes at 8 months post TMEV infection. Co-infection with MCMV influenced the disease course in mice infected prior to TMEV infection. In this group, rotarod detectable motor performance was significantly improved starting 3 months post-infection and beyond (p≤0.024). In addition, their brain atrophy was close to 30% reduced at 8 months, but this was only present as a trend due to low power (p = 0.19). A significant reduction in the proportion of brain infiltrating CD3+ cells was detected in this group (p = 0.026), while the proportion of CD45+ Mac1+ cells significantly increased (p = 0.003). There was also a strong trend for a reduced proportion of CD4+ cells (p = 0.17) while CD8 and B220+ cell proportion did not change. These findings support an immunomodulatory effect of MCMV infection in this MS model. Future studies in this co-infection model will provide insight into mechanisms which modulate the development of demyelination and may be utilized for the development of novel therapeutic strategies.

Original languageEnglish (US)
Article numbere32767
JournalPLoS One
Volume7
Issue number2
DOIs
StatePublished - Feb 29 2012

Fingerprint

Encephalitis Viruses
sclerosis
Viruses
disease course
Multiple Sclerosis
animal models
mice
Infection
Brain
infection
encephalitis
Virus Diseases
Coinfection
viruses
Atrophy
Lymphocytes
brain
Demyelinating Diseases
Magnetic resonance imaging
atrophy

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Pirko, I., Cardin, R., Chen, Y., Lohrey, A. K., Lindquist, D. M., Dunn, R. S., ... Johnson, A. J. (2012). CMV infection attenuates the disease course in a murine model of multiple sclerosis. PLoS One, 7(2), [e32767]. https://doi.org/10.1371/journal.pone.0032767

CMV infection attenuates the disease course in a murine model of multiple sclerosis. / Pirko, Istvan; Cardin, Rhonda; Chen, Yi; Lohrey, Anne K.; Lindquist, Diana M.; Dunn, R. Scott; Zivadinov, Robert; Johnson, Aaron J.

In: PLoS One, Vol. 7, No. 2, e32767, 29.02.2012.

Research output: Contribution to journalArticle

Pirko, I, Cardin, R, Chen, Y, Lohrey, AK, Lindquist, DM, Dunn, RS, Zivadinov, R & Johnson, AJ 2012, 'CMV infection attenuates the disease course in a murine model of multiple sclerosis', PLoS One, vol. 7, no. 2, e32767. https://doi.org/10.1371/journal.pone.0032767
Pirko I, Cardin R, Chen Y, Lohrey AK, Lindquist DM, Dunn RS et al. CMV infection attenuates the disease course in a murine model of multiple sclerosis. PLoS One. 2012 Feb 29;7(2). e32767. https://doi.org/10.1371/journal.pone.0032767
Pirko, Istvan ; Cardin, Rhonda ; Chen, Yi ; Lohrey, Anne K. ; Lindquist, Diana M. ; Dunn, R. Scott ; Zivadinov, Robert ; Johnson, Aaron J. / CMV infection attenuates the disease course in a murine model of multiple sclerosis. In: PLoS One. 2012 ; Vol. 7, No. 2.
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