ArticleProceedings of the National Academy of Sciences of the United States of America2008
CXCR4 antagonism increases T cell trafficking in the central nervous system and improves survival from West Nile virus encephalitis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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Who cites it
96 citing papers in PubMed, 147 citations in OpenAlex.
- Article
- Evaluation of CXCL12 Diagnostic Performance in Tick-Borne Encephalitis and Other Central Nervous System Infections.International journal of molecular sciences · 2026Article
- Pathogenic breaches: how viruses compromise blood-tissue barriers.Tissue barriers · 2026Review
- Unraveling the complexities of neurotropic virus infection and immune evasion.Microbiology and molecular biology reviews : MMBR · 2025Review
- In vivo genome-wide CRISPR screens in human T cells to enhance T cell therapy for solid tumors.bioRxiv : the preprint server for biology · 2025Article
- Astrocytic RIPK3 exerts protective anti-inflammatory activity in mice with viral encephalitis by transcriptional induction of serpins.Science signaling · 2025Article
- Live long and persist: polyomavirus immune evasion in the brain and kidney.Future virology · 2025Article
- CXCR4 and CXCR6 dually limit T cell entry into the polyomavirus-infected brain.Journal of neuroinflammation · 2025Article
- Leukocyte recruitment in flavivirus-induced encephalitis.Frontiers in immunology · 2025Review
- Knowns and unknowns of TiLV-associated neuronal disease.Virulence · 2024Review
- Orchestration of antiviral responses within the infected central nervous system.Cellular & molecular immunology · 2024Review
- Plerixafor for pathogen-agnostic treatment in murine thigh infection and zebrafish sepsis.Clinical and translational science · 2024Article
- Distinct fibroblast functions associated with fibrotic and immune-mediated inflammatory diseases and their implications for therapeutic development.F1000Research · 2024Review
- Polygenic risk associated with Alzheimer's disease and other traits influences genes involved in T cell signaling and activation.Frontiers in immunology · 2024Article
- A Pocket Guide to CCR5-Neurotropic Flavivirus Edition.Viruses · 2023Review
- Effects of a Small-Molecule Perforin Inhibitor in a Mouse Model of CD8 T Cell-Mediated Neuroinflammation.Neurology(R) neuroimmunology & neuroinflammation · 2023Article
- Interleukins, Chemokines, and Tumor Necrosis Factor Superfamily Ligands in the Pathogenesis of West Nile Virus Infection.Viruses · 2023Review
- Immune responses to Tilapia lake virus infection: what we know and what we don't know.Frontiers in immunology · 2023Review
- Pharmacological perturbation of CXCL1 signaling alleviates neuropathogenesis in a model of HEVA71 infection.Nature communications · 2022Article
- The increased intrathecal expression of the monocyte-attracting chemokines CCL7 and CXCL12 in tick-borne encephalitis.Journal of neurovirology · 2021Article
36 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
The migration of lymphocytes into the CNS during viral encephalitis is hindered by the blood-brain barrier (BBB) such that most infiltrating cells remain localized to perivascular spaces. This sequestration of leukocytes away from the parenchyma is believed to protect the CNS from immunopathologic injury. Infections of the CNS with highly cytopathic neurotropic viruses, such as West Nile virus (WNV), however, require the parenchymal penetration of T lymphocytes for virus clearance and survival, suggesting that perivascular localization might hinder antiviral immune responses during WNV encephalitis. Using human and murine brain specimens from individuals with WNV encephalitis, we evaluated the expression of CXCL12 and its receptor, CXCR4, at the BBB and tested the hypothesis that inhibition of CXCR4 would promote T lymphocyte entry into the CNS parenchyma and increase viral clearance. Antagonism of CXCR4 significantly improved survival from lethal infection through enhanced intraparenchymal migration of WNV-specific CD8(+) T cells within the brain, leading to reduced viral loads and, surprisingly, decreased immunopathology at this site. The benefits of enhanced CD8(+) T cell infiltration suggest that pharmacologic targeting of CXCR4 may have therapeutic utility for the treatment of acute viral infections of the CNS.
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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.