Microtubule remodeling by the innate immune factor Trim69 compromises dynein-dependent migration of HIV virion cores toward the nucleus
Open accessPublished version of a preprint
Abstract
Like many viruses, HIV relies on the microtubule (MT) cytoskeleton for successful infection. MT-associated proteins (MAPs) regulate MT functions and thus bear the potential to modulate viral infection. However, while several MAPs are known to exert proviral effects on HIV, little is known about antiviral ones. We previously described the Tripartite motif protein 69 (Trim69) as an innate immune factor that remodels MTs, leading to inhibition of a broad spectrum of viruses, including HIV. Through in silico modeling, TIRF microscopy, and cell-based assays, we determine that Trim69 binding to MTs is determined by a basic surface in its SPRY domain that interacts with the C-terminal tails of tubulins. This surface is conserved among mammalian Trim69s and is critical for its functions. We demonstrate that by binding and remodeling MTs, Trim69 inhibits the docking and the migration of virion cores on MTs by promoting the stalling of the dynein/dynactin motor complexes. Altogether, these findings shed light on a mechanism of viral defense that involves an innate immune regulation of the MT cytoskeleton.
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Cites
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- Authors
- Vadon, C., Nguyen, X.-N., Siahaan, V., Song, Y., Krishnan, A., Henriot, V., Chantharath, A., Burlaud-Gaillard, J., Roingeard, P., Janke, C., Etienne, L., Fiorini, F., Magiera, M. M., & Cimarelli, A.
- Affiliations
- Lyon 1 Université (FR)
- Centre National de la Recherche Scientifique (FR)
- Institut Curie, Université Paris Sciences et lettres, CNRS UMR3348
- Plateforme Infrastructures en Biologie Sante et Agronomie de Microscopie Electronique, Université de Tours et Centre Hospitalier Universitaire de Tours
- Université de Tours (FR)
- Corresponding author
- Vadon, Charlotte
- Nguyen, Xuan-Nhi
- Cimarelli, Andrea
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2025-10-09
- Volume
- 122
- Issue
- 41
- Pages
- e2505128122-e2505128122
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W4414987340
- Cited by
- 1
- References
- 4
- Citations by year
- 2026: 1
- FWCI
- 0.50
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by-nc-nd)
- HAL (submittedVersion)
- Funders
- Agence Nationale de Recherches sur le Sida et les Hépatites Virales (AO-2021-1 ECTZ162940, AO-2021-1 ECTZ160109 and ANRS0644)
- Sidaction (AO2024)
- Agence Nationale de la Recherche (ANR-24-CE15-2986)
- EC | European Research Council (TubulinCode)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- microtubule remodeling, microtubule-associated proteins, antiviral innate immunity, tubulin C-terminal tails, SPRY domain, HIV infection, microtubule cytoskeleton
- MeSH terms
- Tripartite Motif Proteins, Cell Nucleus, Dyneins, Humans, Immunity, Innate, Microtubule-Associated Proteins, Microtubules, Protein Binding, Virion, HIV-1, HIV Infections, Ubiquitin-Protein Ligases
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