ArticleNeurobiology of disease2016
The Janus kinase inhibitor ruxolitinib reduces HIV replication in human macrophages and ameliorates HIV encephalitis in a murine model.
Article in Neurobiology of disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 83 citations in OpenAlex.
- Study protocol for neuroimaging using 7 T MRI in the investigation of baricitinib for reduction of HIV in the CNS: a randomized placebo-controlled trial.BMC medical imaging · 2026Trial
- Ruxolitinib Penetrates Blood Brain Barrier and Reduces the Cytokine Storm in Patients With Haemophagocytic Lymphohistiocytosis.Journal of cellular and molecular medicine · 2026Article
- Acute psychosis following initiation of ruxolitinib in post-polycythaemia vera myelofibrosis case report.Annals of hematology · 2026Article
- Interferon signaling pathways in health and disease.Molecular biomedicine · 2025Review
- JAK1/2 Inhibition Delays Cachexia and Improves Survival through Increased Food Intake.bioRxiv : the preprint server for biology · 2025Article
- Review
- Pathway-instructed therapeutic selection of ruxolitinib reduces neuroinflammation in fungal postinfectious inflammatory syndrome.Science advances · 2025Observational
- Ruxolitinib-dependent reduction of seizure load and duration is accompanied by spatial memory improvement in the rat pilocarpine model of temporal lobe epilepsy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Experimental and clinical tests of FDA-approved kinase inhibitors for the treatment of neurological disorders (update 2024).Exploration of drug science · 2025Article
- Therapeutic targeting of senescent cells in the CNS.Nature reviews. Drug discovery · 2024Review
- Dual inhibition of the TrkA and JAK2 pathways using entrectinib and pacritinib suppresses the growth and metastasis of HER2-positive and triple-negative breast cancers.Cancer letters · 2024Article
- The interferon-regulated host factor hnRNPA0 modulates HIV-1 production by interference with LTR activity, mRNA trafficking, and programmed ribosomal frameshifting.Journal of virology · 2024Article
- JAK/STAT signaling pathway affects CCR5 expression in human CD4Science advances · 2024Article
- Ruxolitinib-based regimen in children with primary hemophagocytic lymphohistiocytosis.Haematologica · 2024Article
- Integrated genetic analyses of immunodeficiency-associated Epstein-Barr virus- (EBV) positive primary CNS lymphomas.Acta neuropathologica · 2023Article
- Mitigating neurological, cognitive, and psychiatric sequelae of COVID-19-related critical illness.The Lancet. Respiratory medicine · 2023Review
- An improved reporter identifies ruxolitinib as a potent and cardioprotective CaMKII inhibitor.Science translational medicine · 2023Article
- Review
- Prevention of Chemotherapy-Induced Peripheral Neuropathy by Inhibiting C-X-C Motif Chemokine Receptor 2.International journal of molecular sciences · 2023Article
- Anti-inflammatory compounds reduce equine herpesvirus type 1 replication and cell-to-cell spread.Frontiers in veterinary science · 2023Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
A hallmark of persistent HIV-1 infection in the central nervous system is increased activation of mononuclear phagocytes and surrounding astrogliosis, conferring persistent HIV-induced inflammation. This inflammation is believed to result in neuronal dysfunction and the clinical manifestations of HIV-associated neurocognitive disorders (HAND). The Jak/STAT pathway is activated in macrophages/myeloid cells upon HIV-1 infection, modulating many pro-inflammatory pathways that result in HAND, thereby representing an attractive cellular target. Thus, the impact of ruxolitinib, a Janus Kinase (Jak) 1/2 inhibitor that is FDA approved for myelofibrosis and polycythemia vera, was assessed for its potential to inhibit HIV-1 replication in macrophages and HIV-induced activation in monocytes/macrophages in culture. In addition, a murine model of HIV encephalitis (HIVE) was used to assess the impact of ruxolitinib on histopathological features of HIVE, brain viral load, as well as its ability to penetrate the blood-brain-barrier (BBB). Ruxolitinib was found to inhibit HIV-1 replication in macrophages, HIV-induced activation of monocytes (CD14/CD16) and macrophages (HLA-DR, CCR5, and CD163) without apparent toxicity. In vivo, systemically administered ruxolitinib was detected in the brain during HIVE in SCID mice and markedly inhibited astrogliosis. Together, these data indicate that ruxolitinib reduces HIV-induced activation and infiltration of monocytes/macrophages in vitro, reduces the replication of HIV in vitro, penetrates the BBB when systemically administered in mice and reduces astrogliosis in the brains of mice with HIVE. These data suggest that ruxolitinib will be useful as a novel therapeutic to treat humans with HAND.
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