ArticleJournal of neurovirology2015
Neurological sequelae induced by alphavirus infection of the CNS are attenuated by treatment with the glutamine antagonist 6-diazo-5-oxo-l-norleucine.
Article in Journal of neurovirology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 28 citations in OpenAlex.
- Molecular evidence of neuroinvasive Sindbis virus infection in humans: detection in cerebrospinal fluid by next generation sequencing.Emerging microbes & infections · 2026Article
- Differentiated LUHMES Cells as a Model to Investigate Neurotropic Arboviruses and Evaluate Host-Directed Therapeutics.Microorganisms · 2026Article
- Characterization of an immunocompetent, young adult mouse model for studying chikungunya virus neuroinvasion and central nervous system infection.PLoS pathogens · 2026Article
- Neurotropic alphavirus infection induces PARP-1 hyperactivation-mediated energy collapse in motor neurons.Journal of virology · 2026Article
- Arbovirus infection increases the risk for the development of neurodegenerative disease pathology in the murine model.Brain, behavior, & immunity - health · 2024Article
- Chronic cerebral aspects of long COVID, post-stroke syndromes and similar states share their pathogenesis and perispinal etanercept treatment logic.Pharmacology research & perspectives · 2022Review
- Modulating glutamine metabolism to control viral immuno-inflammatory lesions.Cellular immunology · 2021Article
- Implications of Innate Immunity in Post-Acute Sequelae of Non-Persistent Viral Infections.Cells · 2021Review
- The Novel Glutamine Antagonist Prodrug JHU395 Has Antitumor Activity in Malignant Peripheral Nerve Sheath Tumor.Molecular cancer therapeutics · 2020Article
- Immunopathogenesis of alphaviruses.Advances in virus research · 2020Article
- Metabolic Pathways in Alloreactive T Cells.Frontiers in immunology · 2020Review
- JHU-083 selectively blocks glutaminase activity in brain CD11bNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Article
- Inhibition of glutamine metabolism accelerates resolution of acute lung injury.Physiological reports · 2019Article
- MRI demonstrates glutamine antagonist-mediated reversal of cerebral malaria pathology in mice.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Genetic control of alphavirus pathogenesis.Mammalian genome : official journal of the International Mammalian Genome Society · 2018Review
- Germ Line IgM Is Sufficient, but Not Required, for Antibody-Mediated Alphavirus Clearance from the Central Nervous System.Journal of virology · 2018Article
- Interleukin-10 Modulation of Virus Clearance and Disease in Mice with Alphaviral Encephalomyelitis.Journal of virology · 2018Article
- Death and gastrointestinal bleeding complicate encephalomyelitis in mice with delayed appearance of CNS IgM after intranasal alphavirus infection.The Journal of general virology · 2018Article
- N-(Pivaloyloxy)alkoxy-carbonyl Prodrugs of the Glutamine Antagonist 6-Diazo-5-oxo-l-norleucine (DON) as a Potential Treatment for HIV Associated Neurocognitive Disorders.Journal of medicinal chemistry · 2017Article
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Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Recovery from encephalomyelitis induced by infection with mosquito-borne alphaviruses is associated with a high risk of lifelong debilitating neurological deficits. Infection of mice with the prototypic alphavirus, Sindbis virus, provides an animal model with which to study disease mechanisms and examine potential therapeutics. Infectious virus is cleared from the brain within a week after infection, but viral RNA is cleared slowly and persists for the life of the animal. However, no studies have examined the effect of infection on neurocognitive function over time. In the present study, we examined neurocognitive function at different phases of infection in 5-week-old C57BL/6 mice intranasally inoculated with Sindbis virus. At the peak of active virus infection, mice demonstrated hyperactivity, decreased anxiety, and marked hippocampal-dependent memory deficits, the latter of which persisted beyond clearance of infectious virus and resolution of clinical signs of disease. Previous studies indicate that neuronal damage during alphavirus encephalomyelitis is primarily due to inflammatory cell infiltration and glutamate excitotoxicity rather than directly by virus infection. Therefore, mice were treated with 6-diazo-5-oxo-l-norleucine (DON), a glutamine antagonist that can suppress both the immune response and excitotoxicity. Treatment with DON decreased inflammatory cell infiltration and cell death in the hippocampus and partially prevented development of clinical signs and neurocognitive impairment despite the presence of infectious virus and high viral RNA levels. This study presents the first report of neurocognitive sequelae in mice with alphavirus encephalomyelitis and provides a model system for further elucidation of the pathogenesis of virus infection and assessment of potential therapies.
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