ArticleThe Journal of clinical investigation2024
CDKL5 regulates p62-mediated selective autophagy and confers protection against neurotropic viruses.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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
14 citing papers in PubMed, 15 citations in OpenAlex.
- Review
- CDKL5 deficiency impairs TBK1-mediated autophagy and clearance of neuronal protein aggregates.bioRxiv : the preprint server for biology · 2026Article
- The oncogenic signalosome: SQSTM1/p62 as a master integrator of signaling, metabolism, and autophagy in cancer.Toxicological research · 2026Review
- CMGC Kinases in Viral Infection and Human Disease.Pathogens (Basel, Switzerland) · 2026Review
- Post-translational modifications of selective autophagy receptors: orchestrating cellular homeostasis, disease pathogenesis, and therapeutic opportunities.Cellular & molecular biology letters · 2026Review
- The Roles of SQSTM1/p62 in Selective Autophagy and Oncogenic Signaling.International journal of molecular sciences · 2026Review
- Role of autophagy in antiviral innate immunity.Cellular & molecular biology letters · 2026Review
- Host-Microbe Interactions: Understanding the Mechanism of Autophagy in Viral Replication and Immune Evasion.Veterinary sciences · 2025Review
- Mammalian innate antiviral defenses: beyond interferon.Journal of virology · 2025Review
- CDKL5 Deficiency Disorder: Revealing the Molecular Mechanism of Pathogenic Variants.International journal of molecular sciences · 2025Article
- Direct pharmacological AMPK activation inhibits mucosal SARS-CoV-2 infection by reducing lipid metabolism, restoring autophagy flux and the type I IFN response.Journal of virology · 2025Article
- Review
- The role of HDAC11 in age-related hearing loss: Mechanisms and therapeutic implications.Open life sciences · 2025Article
- The multifaceted roles of selective autophagy receptors in viral infections.Journal of virology · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
Abstract
Virophagy, the selective autophagosomal engulfment and lysosomal degradation of viral components, is crucial for neuronal cell survival and antiviral immunity. However, the mechanisms leading to viral antigen recognition and capture by autophagic machinery remain poorly understood. Here, we identified cyclin-dependent kinase-like 5 (CDKL5), known to function in neurodevelopment, as an essential regulator of virophagy. Loss-of-function mutations in CDKL5 are associated with a severe neurodevelopmental encephalopathy. We found that deletion of CDKL5 or expression of a clinically relevant pathogenic mutant of CDKL5 reduced virophagy of Sindbis virus (SINV), a neurotropic RNA virus, and increased intracellular accumulation of SINV capsid protein aggregates and cellular cytotoxicity. Cdkl5-knockout mice displayed increased viral antigen accumulation and neuronal cell death after SINV infection and enhanced lethality after infection with several neurotropic viruses. Mechanistic studies demonstrated that CDKL5 directly binds the canonical selective autophagy receptor p62 and phosphorylates p62 at T269/S272 to promote its interaction with viral capsid aggregates. We found that CDKL5-mediated phosphorylation of p62 facilitated the formation of large p62 inclusion bodies that captured viral capsids to initiate capsid targeting to autophagic machinery. Overall, these findings identify a cell-autonomous innate immune mechanism for autophagy activation to clear intracellular toxic viral protein aggregates during infection.
Indexed as
Identifiers
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.