ArticleNature2016
A complement-microglial axis drives synapse loss during virus-induced memory impairment.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 422 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
422 citing papers in PubMed, 3 syntheses or guidelines pooled it, 666 citations in OpenAlex.
- Effects of herpes zoster infection, antivirals and vaccination on risk of developing dementia: A systematic review and meta-analysis.Human vaccines & immunotherapeutics · 2025Pooled it
- Pooled it
- Frequency and Focus of in Vitro Studies of Microglia-Expressed Cytokines in Response to Viral Infection: A Systematic Review.Cellular and molecular neurobiology · 2024Pooled it
- Microglial states revisited: from homeostasis to disease.Nature reviews. Neuroscience · 2026Review
- Synthetic viral RNA mimetics induce neuronal loss through microglial phagocytosis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Article
- Microglia and neuroinflammation: function, heterogeneity, and crosstalk.Cellular & molecular immunology · 2026Review
- Human IL-34 Deficiency Primes Microglia Toward Alzheimer's Disease-Associated States.medRxiv : the preprint server for health sciences · 2026Article
- Microglial ITAM & ITIM Signaling in Neurodegenerative Disease and Brain Aging.Journal of molecular biology · 2026Review
- Spatially Stereotyped Microgliosis Tracks Synaptic Pathology in the Demyelinated Superior Colliculus.Research square · 2026Article
- Differential selectivity of microglia and astrocytes in HIV-1 gp120-induced synaptic pruning.Brain : a journal of neurology · 2026Article
- NOD2 activation reprograms infiltrating inflammatory monocytes in the Zika virus infected CNS to maintain neural correlates of learning and memory.bioRxiv : the preprint server for biology · 2026Article
- Potential Protection Against Parkinson's Disease by Ergothioneine-Nature's Multifactorial Neuroprotectant.Antioxidants (Basel, Switzerland) · 2026Review
- Timing of microglial ablation determines protection from tau-mediated neurodegeneration and cognitive decline.Acta neuropathologica communications · 2026Article
- Venezuelan equine encephalitis virus infection causes chronic neurobehavioral outcomes, cellular remodeling, and hippocampal single-cell transcriptomic changes.PLoS pathogens · 2026Article
- Neural Stem Cell-Derived Exosomes-Transmitted miR-31-5p Promote Functional Recovery of Spinal Cord Injury by Shifting Astrocytes A1/A2 Polarization.Molecular neurobiology · 2026Article
- Herpes simplex virus-1 induces complement-mediated microglial phagocytosis of synapses in murine primary brain cultures and tissues.Cell communication and signaling : CCS · 2026Article
- Viral modulation of synaptic pruning: implications for neuropathology and brain function.Journal of virology · 2026Review
- A sex-biased response of the adult brain to Zika virus infection: from down-regulation of neuronal IRF3 to enhanced pathology in adult female mice.Cell communication and signaling : CCS · 2026Article
- Targeting neuroinflammation: itaconate and mesaconate as therapeutic strategies against H7N7 influenza-associated CNS damage.Frontiers in immunology · 2026Article
362 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 5 institutions in 1 country.
Funding
Abstract
Over 50% of patients who survive neuroinvasive infection with West Nile virus (WNV) exhibit chronic cognitive sequelae. Although thousands of cases of WNV-mediated memory dysfunction accrue annually, the mechanisms responsible for these impairments are unknown. The classical complement cascade, a key component of innate immune pathogen defence, mediates synaptic pruning by microglia during early postnatal development. Here we show that viral infection of adult hippocampal neurons induces complement-mediated elimination of presynaptic terminals in a murine WNV neuroinvasive disease model. Inoculation of WNV-NS5-E218A, a WNV with a mutant NS5(E218A) protein leads to survival rates and cognitive dysfunction that mirror human WNV neuroinvasive disease. WNV-NS5-E218A-recovered mice (recovery defined as survival after acute infection) display impaired spatial learning and persistence of phagocytic microglia without loss of hippocampal neurons or volume. Hippocampi from WNV-NS5-E218A-recovered mice with poor spatial learning show increased expression of genes that drive synaptic remodelling by microglia via complement. C1QA was upregulated and localized to microglia, infected neurons and presynaptic terminals during WNV neuroinvasive disease. Murine and human WNV neuroinvasive disease post-mortem samples exhibit loss of hippocampal CA3 presynaptic terminals, and murine studies revealed microglial engulfment of presynaptic terminals during acute infection and after recovery. Mice with fewer microglia (Il34(-/-) mice with a deficiency in IL-34 production) or deficiency in complement C3 or C3a receptor were protected from WNV-induced synaptic terminal loss. Our study provides a new murine model of WNV-induced spatial memory impairment, and identifies a potential mechanism underlying neurocognitive impairment in patients recovering from WNV neuroinvasive disease.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.