title: Critical role for the kinesin KIF3A in the HIV life cycle in primary human macrophages.
abstract: Macrophages are long-lived target cells for HIV infection and are considered viral reservoirs. HIV assembly in macrophages occurs in virus-containing compartments (VCCs) in which virions accumulate and are stored. The regulation of the trafficking and release of these VCCs remains unknown. Using high resolution light and electron microscopy of HIV-1-infected primary human macrophages, we show that the spatial distribution of VCCs depended on the microtubule network and that VCC-limiting membrane was closely associated with KIF3A+ microtubules. Silencing KIF3A strongly decreased virus release from HIV-1-infected macrophages, leading to VCC accumulation intracellularly. Time-lapse microscopy further suggested that VCCs and associated KIF3A move together along microtubules. Importantly, KIF3A does not play a role in HIV release from T cells that do not possess VCCs. These results reveal that HIV-1 requires the molecular motor KIF3 to complete its cycle in primary macrophages. Targeting this step may lead to novel strategies to eliminate this viral reservoir.
authors.affiliation: Institut Curie, Centre de Recherche, Paris, F-75248 France.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Gaudin
authors.forename: Bruna Cunha
authors.initials: BC
authors.lastname: de Alencar
authors.forename: Mabel
authors.initials: M
authors.lastname: Jouve
authors.forename: Stefano
authors.initials: S
authors.lastname: Bèrre
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Le Bouder
authors.forename: Michael
authors.initials: M
authors.lastname: Schindler
authors.forename: Aditi
authors.initials: A
authors.lastname: Varthaman
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Gobert
authors.forename: Philippe
authors.initials: P
authors.lastname: Benaroch
mesh_terms: D015153:Blotting, Western; D002478:Cells, Cultured; D006678:HIV / Q000502:physiology*; D015658:HIV Infections / Q000821:virology*; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000821:virology*; D008870:Microtubules / Q000821:virology*; D014771:Virion / Q000502:physiology*
chemical_list: C087415:KIF3A protein, human; D016547:Kinesins