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

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 (0.3mg/kg) or high (0.6mg/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.
AuthorsVictoria K Baxter, Rebecca Glowinski, Alicia M Braxton, Michelle C Potter, Barbara S Slusher, Diane E Griffin
JournalVirology (Virology) Vol. 508 Pg. 134-149 (08 2017) ISSN: 1096-0341 [Electronic] United States
PMID28531865 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2017 Elsevier Inc. All rights reserved.
Chemical References
  • Antiviral Agents
  • Diazooxonorleucine
  • Glutamine
  • Interferon-gamma
Topics
  • Alphavirus Infections (drug therapy, immunology, pathology, virology)
  • Animals
  • Antiviral Agents (administration & dosage)
  • Diazooxonorleucine (administration & dosage)
  • Encephalomyelitis (drug therapy, immunology, pathology, virology)
  • Glutamine (antagonists & inhibitors)
  • Humans
  • Interferon-gamma (genetics, immunology)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Sindbis Virus (drug effects, physiology)

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