Reactivation of human herpesvirus-6 in natalizumab treated multiple sclerosis patients

Karen Yao, Susan Gagnon, Nahid Akhyani, Elizabeth Williams, Julie Fotheringham, Elliot Frohman, Olaf Stuve, Nancy L Monson, Michael K. Racke, Steven Jacobson

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

The α4 integrin antagonist natalizumab was shown to be effective in patients with immune-mediated disorders but was unexpectedly associated with JC polyomavirus associated progressive multifocal leukoencephalopahty (PML) in two multiple sclerosis (MS) and one Crohn's disease patients. Impaired immune surveillance due to natalizumab treatment may have contributed to the JCV reactivation. As HHV-6 has been suggested to play a role in MS, we asked whether this virus could also have been reactivated during natalizumab therapy. Matched sera and CSF from a limited set of MS patients treated with and without natalizumab were examined for evidence of HHV-6. In Addition, we also superinfected a persistent JC virus infected glial cell with HHV-6A to determine if JC virus can be increased. Elevated serum HHV6 IgG and HHV-6A DNA was detected in the CSF of a subser of patients but not controls. We confirmed that superinfection with HHV-6 of a JC virus infected glial cells increased expression of JCV. These results support the hypothesis that treatment with natalizumab may be associated with reduced immune surveillance resulting in reactivation of viruses associated with MS pathogenesis.

Original languageEnglish (US)
Article numbere2028
JournalPloS one
Volume3
Issue number4
DOIs
StatePublished - Apr 30 2008

ASJC Scopus subject areas

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

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    Yao, K., Gagnon, S., Akhyani, N., Williams, E., Fotheringham, J., Frohman, E., Stuve, O., Monson, N. L., Racke, M. K., & Jacobson, S. (2008). Reactivation of human herpesvirus-6 in natalizumab treated multiple sclerosis patients. PloS one, 3(4), [e2028]. https://doi.org/10.1371/journal.pone.0002028