Microtubule remodeling by the innate immune factor Trim69 compromises dynein-dependent migration of HIV virion cores toward the nucleus
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.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (14)
Charlotte Vadon
Centre International de Recherche en Infectiologie, Université de Lyon, INSERM, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, École Nationale Supérieure de Lyon
Xuan-Nhi Nguyen
Centre International de Recherche en Infectiologie, Université de Lyon, INSERM, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, École Nationale Supérieure de Lyon
Valerie Siahaan
Institut Curie, Université Paris Sciences et lettres, CNRS UMR3348
Yuxin Song
Arya Krishnan
Institut Curie, Université Paris Sciences et lettres, CNRS UMR3348
Veronique Henriot
Institut Curie, Université Paris Sciences et lettres, CNRS UMR3348
Amandine Chantharath
Centre International de Recherche en Infectiologie, Université de Lyon, INSERM, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, École Nationale Supérieure de Lyon
Julien Burlaud-Gaillard
Plateforme Infrastructures en Biologie Sante et Agronomie de Microscopie Electronique, Université de Tours et Centre Hospitalier Universitaire de Tours
Philippe Roingeard
Plateforme Infrastructures en Biologie Sante et Agronomie de Microscopie Electronique, Université de Tours et Centre Hospitalier Universitaire de Tours
Carsten Janke
Institut Curie, Université Paris Sciences et lettres, CNRS UMR3348
Lucie Etienne
Centre International de Recherche en Infectiologie, Université de Lyon, INSERM, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, École Nationale Supérieure de Lyon
Francesca Fiorini
Molecular Microbiology and Structural Biochemistry, Microbiologie Moléculaire et Biochimie Structurale-Institut de Biologie et de Chimie des Protéines, UMR 5086 CNRS University of Lyon
Maria M. Magiera
Institut Curie, Université Paris Sciences et lettres, CNRS UMR3348
Andrea Cimarelli
Centre International de Recherche en Infectiologie, Université de Lyon, INSERM, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, École Nationale Supérieure de Lyon