title: Microtubule-associated proteins 1 (MAP1) promote human immunodeficiency virus type I (HIV-1) intracytoplasmic routing to the nucleus.
abstract: After cell entry, HIV undergoes rapid transport toward the nucleus using microtubules and microfilaments. Neither the cellular cytoplasmic components nor the viral proteins that interact to mediate transport have yet been identified. Using a yeast two-hybrid screen, we identified four cytoskeletal components as putative interaction partners for HIV-1 p24 capsid protein: MAP1A, MAP1S, CKAP1, and WIRE. Depletion of MAP1A/MAP1S in indicator cell lines and primary human macrophages led to a profound reduction in HIV-1 infectivity as a result of impaired retrograde trafficking, demonstrated by a characteristic accumulation of capsids away from the nuclear membrane, and an overall defect in nuclear import. MAP1A/MAP1S did not impact microtubule network integrity or cell morphology but contributed to microtubule stabilization, which was shown previously to facilitate infection. In addition, we found that MAP1 proteins interact with HIV-1 cores both in vitro and in infected cells and that interaction involves MAP1 light chain LC2. Depletion of MAP1 proteins reduced the association of HIV-1 capsids with both dynamic and stable microtubules, suggesting that MAP1 proteins help tether incoming viral capsids to the microtubular network, thus promoting cytoplasmic trafficking. This work shows for the first time that following entry into target cells, HIV-1 interacts with the cytoskeleton via its p24 capsid protein. Moreover, our results support a role for MAP1 proteins in promoting efficient retrograde trafficking of HIV-1 by stimulating the formation of stable microtubules and mediating the association of HIV-1 cores with microtubules.
authors.affiliation: From INSERM U941, Institut Universitaire d'Hématologie de l'Hôpital Saint-Louis, 75010 Paris, France.
authors.forename: Juliette
authors.initials: J
authors.lastname: Fernandez
authors.affiliation: From INSERM U941, Institut Universitaire d'Hématologie de l'Hôpital Saint-Louis, 75010 Paris, France.
authors.forename: Débora M
authors.initials: DM
authors.lastname: Portilho
authors.affiliation: Imagopole, Institut Pasteur, 75015 Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Danckaert
authors.affiliation: the Département de Virologie, Unité de Génétique Moléculaire des Virus à ARN, Université Paris Diderot, CNRS UMR3569, Institut Pasteur, 75015 Paris, France.
authors.forename: Sandie
authors.initials: S
authors.lastname: Munier
authors.affiliation: From INSERM U941, Institut Universitaire d'Hématologie de l'Hôpital Saint-Louis, 75010 Paris, France.
authors.forename: Andreas
authors.initials: A
authors.lastname: Becker
authors.affiliation: Imagopole, Institut Pasteur, 75015 Paris, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Roux
authors.affiliation: From INSERM U941, Institut Universitaire d'Hématologie de l'Hôpital Saint-Louis, 75010 Paris, France.
authors.forename: Anaba
authors.initials: A
authors.lastname: Zambo
authors.affiliation: Imagopole, Institut Pasteur, 75015 Paris, France.
authors.forename: Spencer
authors.initials: S
authors.lastname: Shorte
authors.affiliation: the Département de Virologie, Unité de Génétique Moléculaire des Virus à ARN, Université Paris Diderot, CNRS UMR3569, Institut Pasteur, 75015 Paris, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Jacob
authors.affiliation: Unité de Génomique Virale et Vaccination, CNRS UMR3569, Institut Pasteur, 75015 Paris, France, and.
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Vidalain
authors.affiliation: the Unité de Virologie Moléculaire et Vaccinologie, Institut Pasteur, 75015 Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Charneau
authors.affiliation: From INSERM U941, Institut Universitaire d'Hématologie de l'Hôpital Saint-Louis, 75010 Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Clavel
authors.affiliation: From INSERM U941, Institut Universitaire d'Hématologie de l'Hôpital Saint-Louis, 75010 Paris, France,. Electronic address: nathalie.arhel@inserm.fr.
authors.forename: Nathalie J
authors.initials: NJ
authors.lastname: Arhel
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D016655:HIV Core Protein p24 / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D002352:Carrier Proteins; D016655:HIV Core Protein p24; C093429:MAP1A protein, human; C493240:MAP1S protein, human; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; C465744:WIPF2 protein, human; C514799:p24 protein, Human Immunodeficiency Virus Type 1
keywords: Cytoskeleton; Human Immunodeficiency Virus (HIV); Microtubule; Transport; Virology