Glutamine antagonist-mediated immune suppression decreases pathology but delays virus clearance in mice during nonfatal alphavirus encephalomyelitis

Victoria K. Baxter, Rebecca Glowinski, Alicia M. Braxton, Michelle C. Potter, Barbara S. Slusher, Diane E. Griffin

Research output: Contribution to journalArticle

Abstract

Infection of weanling C57BL/6 mice with the TE strain of Sindbis virus (SINV) causes nonfatal encephalomyelitis associated with hippocampal-based memory impairment that is partially prevented by treatment with 6-diazo-5-oxo-l-norleucine (DON), a glutamine antagonist (Potter et al., J Neurovirol 21:159, 2015). To determine the mechanism(s) of protection, lymph node and central nervous system (CNS) tissues from SINV-infected mice treated daily for 1 week with low (0.3 mg/kg) or high (0.6 mg/kg) dose DON were examined. DON treatment suppressed lymphocyte proliferation in cervical lymph nodes resulting in reduced CNS immune cell infiltration, inflammation, and cell death compared to untreated SINV-infected mice. Production of SINV-specific antibody and interferon-gamma were also impaired by DON treatment with a delay in virus clearance. Cessation of treatment allowed activation of the antiviral immune response and viral clearance, but revived CNS pathology, demonstrating the ability of the immune response to mediate both CNS damage and virus clearance.

Original languageEnglish (US)
Pages (from-to)134-149
Number of pages16
JournalVirology
Volume508
DOIs
StatePublished - Aug 2017

Keywords

  • 6-diazo-5-oxo-l-norleucine
  • Alphavirus encephalomyelitis
  • Glutamate excitotoxicity
  • Immune response
  • Sindbis virus
  • Viral pathogenesis

ASJC Scopus subject areas

  • Virology

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