ArticleJournal of neurovirology2015
Quinolinic acid/tryptophan ratios predict neurological disease in SIV-infected macaques and remain elevated in the brain under cART.
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 23 papers.
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Who cites it
23 citing papers in PubMed, 55 citations in OpenAlex.
- Exploratory Cohort Study of Depressive Symptoms in South Africans with HIV-1 Subtype C: Associations with Kynurenine Pathway Metabolites and Inflammatory Markers.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Article
- Quinolinic acid potentially links kidney injury to brain toxicity.JCI insight · 2025Article
- Prepandemic Metabolic Correlates of Coronavirus Disease 2019 (COVID-19) Severity and Long COVID Incidence in People Living With HIV.The Journal of infectious diseases · 2024Article
- Neuroactive Kynurenines as Pharmacological Targets: New Experimental Tools and Exciting Therapeutic Opportunities.Pharmacological reviews · 2024Review
- Pathological shifts in tryptophan metabolism in human term placenta exposed to LPS or poly I:C†.Biology of reproduction · 2024Article
- Distinct intestinal microbial signatures linked to accelerated systemic and intestinal biological aging.Microbiome · 2024Article
- Markers of fungal translocation are elevated during post-acute sequelae of SARS-CoV-2 and induce NF-κB signaling.JCI insight · 2022Article
- Advances in SIV/SHIV Non-Human Primate Models of NeuroAIDS.Pathogens (Basel, Switzerland) · 2021Review
- New Potential Axes of HIV Neuropathogenesis with Relevance to Biomarkers and Treatment.Current topics in behavioral neurosciences · 2021Article
- Abnormal Tryptophan Metabolism in HIV andFrontiers in microbiology · 2021Review
- Circulating levels of ATP is a biomarker of HIV cognitive impairment.EBioMedicine · 2020Article
- Encephalitis and aseptic meningitis: short-term and long-term outcome, quality of life and neuropsychological functioning.Scientific reports · 2019Observational
- HIV infection and latency induce a unique metabolic signature in human macrophages.Scientific reports · 2019Article
- Effects of HIV-1 TAT protein and methamphetamine exposure on visual discrimination and executive function in mice.Behavioural brain research · 2018Article
- HIV, prospective memory, and cerebrospinal fluid concentrations of quinolinic acid and phosphorylated Tau.Journal of neuroimmunology · 2018Article
- Crystal structures of human 3-hydroxyanthranilate 3,4-dioxygenase with native and non-native metals bound in the active site.Acta crystallographica. Section D, Structural biology · 2017Article
- Review
- Maternal Inflammation Results in Altered Tryptophan Metabolism in Rabbit Placenta and Fetal Brain.Developmental neuroscience · 2017Article
- Metabolic profiling during HIV-1 and HIV-2 infection of primary human monocyte-derived macrophages.Virology · 2016Article
- Distinct Patterns of Tryptophan Maintenance in Tissues during Kynurenine Pathway Activation in Simian Immunodeficiency Virus-Infected Macaques.Frontiers in immunology · 2016Article
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Authors and funding
12 authors at 4 institutions in 1 country.
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Abstract
Activation of the kynurenine pathway (KP) of tryptophan catabolism likely contributes to HIV-associated neurological disorders. However, KP activation in brain tissue during HIV infection has been understudied, and the effect of combination antiretroviral therapy (cART) on KP induction in the brain is unknown. To examine these questions, tryptophan, kynurenine, 3-hydroxykynurenine, quinolinic acid, and serotonin levels were measured longitudinally during SIV infection in the striatum and CSF from untreated and cART-treated pigtailed macaques. Messenger RNA (mRNA) levels of KP enzymes also were measured in the striatum. In untreated macaques, elevations in KP metabolites coincided with transcriptional induction of upstream enzymes in the KP. Striatal KP induction was also temporally associated-but did not directly correlate-with serotonin losses in the brain. CSF quinolinic acid/tryptophan ratios were found to be the earliest predictor of neurological disease in untreated SIV-infected macaques, outperforming other KP metabolites as well as the putative biomarkers interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1). Finally, cART did not restore KP metabolites to control levels in the striatum despite the control of the virus, though CSF metabolite levels were normalized in most animals. Overall, these results demonstrate that cerebral KP activation is only partially resolved with cART and that CSF QUIN/TRP ratios are an early, predictive biomarker of CNS disease.
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