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

Virology
Victoria K BaxterD E Griffin

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.

Citations

Nov 20, 2018·The Journal of General Virology·Kimberly L W SchultzDiane E Griffin
Oct 23, 2019·Frontiers in Microbiology·Deepak SumbriaBarry T Rouse
Aug 29, 2018·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Victoria K Baxter, Mark T Heise
Aug 22, 2018·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Xiaolei ZhuAtsushi Kamiya
Sep 6, 2018·Molecular Neurobiology·Catherine H Schein
Jan 23, 2021·Clinical Science·Sandro Massao HirabaraRui Curi

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
ELISA

Software Mentioned

StereoInvestigator
FlowJo
BD
Sequence Detector
FACSDiva
ImageJ
GraphPad Prism

Related Concepts

Related Feeds

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.