title: HIV-1 capsids bind and exploit the kinesin-1 adaptor FEZ1 for inward movement to the nucleus.
abstract: Intracellular transport of cargos, including many viruses, involves directed movement on microtubules mediated by motor proteins. Although a number of viruses bind motors of opposing directionality, how they associate with and control these motors to accomplish directed movement remains poorly understood. Here we show that human immunodeficiency virus type 1 (HIV-1) associates with the kinesin-1 adaptor protein, Fasiculation and Elongation Factor zeta 1 (FEZ1). RNAi-mediated FEZ1 depletion blocks early infection, with virus particles exhibiting bi-directional motility but no net movement to the nucleus. Furthermore, both dynein and kinesin-1 motors are required for HIV-1 trafficking to the nucleus. Finally, the ability of exogenously expressed FEZ1 to promote early HIV-1 infection requires binding to kinesin-1. Our findings demonstrate that opposing motors both contribute to early HIV-1 movement and identify the kinesin-1 adaptor, FEZ1 as a capsid-associated host regulator of this process usurped by HIV-1 to accomplish net inward movement towards the nucleus.
authors.affiliation: Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.|Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA.
authors.forename: Viacheslav
authors.initials: V
authors.lastname: Malikov
authors.affiliation: Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
authors.forename: Eveline Santos
authors.initials: ES
authors.lastname: da Silva
authors.affiliation: Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Jovasevic
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Bennett
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: de Souza Aranha Vieira
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Bianca
authors.initials: B
authors.lastname: Schulte
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Felipe
authors.initials: F
authors.lastname: Diaz-Griffero
authors.affiliation: Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
authors.forename: Derek
authors.initials: D
authors.lastname: Walsh
authors.affiliation: Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.|Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA.
authors.forename: Mojgan H
authors.initials: MH
authors.lastname: Naghavi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D001692:Biological Transport; D002213:Capsid / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D004398:Dyneins / Q000378:metabolism; D005347:Fibroblasts; D057809:HEK293 Cells; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D016547:Kinesins / Q000378:metabolism; D017628:Microglia; D008870:Microtubules / Q000378:metabolism*; D009000:Monocytes; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D034622:RNA Interference; D013601:T-Lymphocytes
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C528597:FEZ1 protein, human; C488101:KIF5B protein, human; D009419:Nerve Tissue Proteins; D004398:Dyneins; D016547:Kinesins
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