TY - JOUR
T1 - HIV-1 capsids bind and exploit the kinesin-1 adaptor FEZ1 for inward movement to the nucleus
AU - Malikov, Viacheslav
AU - Da Silva, Eveline Santos
AU - Jovasevic, Vladimir
AU - Bennett, Geoffrey
AU - De Souza Aranha Vieira, Daniel A.
AU - Schulte, Bianca
AU - Diaz-Griffero, Felipe
AU - Walsh, Derek
AU - Naghavi, Mojgan H.
N1 - Funding Information:
We thank Edward Campbell, Thomas Hope, David McDonald, Vladimir Gelfand, Geri Kreitzer, Greg Towers, Gregg Gundersen, Hyewon Phee and Chyung-Ru Wang for providing reagents and protocols. The following reagent was obtained through the NIH AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH: H9 and 174xCEM cells; pNL4-3.Luc.R−.E− from Dr Nathaniel Landau. This study was supported by National Institute of Health (NIH) grant GM101975 and GM105536, and a Schaefer Scholarship Award to M.H.N., NIH grant GM105536 to D.W. and NIH grant AI087390 to F.D.-G.
Publisher Copyright:
© 2015, Nature Publishing Group. All rights reserved.
PY - 2015/3
Y1 - 2015/3
N2 - 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.
AB - 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.
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U2 - 10.1038/ncomms7660
DO - 10.1038/ncomms7660
M3 - Article
C2 - 25818806
AN - SCOPUS:84926393829
SN - 2041-1723
VL - 6
JO - Nature Communications
JF - Nature Communications
M1 - 6660
ER -
