HIV-1 capsids bind and exploit the kinesin-1 adaptor FEZ1 for inward movement to the nucleus

• Published in: Nature communications Vol. 6; no. 1; p. 6660
• Main Authors: Malikov, Viacheslav, da Silva, Eveline Santos, Jovasevic, Vladimir, Bennett, Geoffrey, de Souza Aranha Vieira, Daniel A., Schulte, Bianca, Diaz-Griffero, Felipe, Walsh, Derek, Naghavi, Mojgan H.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30-03-2015; Nature Publishing Group
• Subjects: 13; 14; 38; 42; 631/326/596/2148; 631/80/128/1653; 631/80/128/2343; 692/699/255/1901; 82; 96; Adaptor Proteins, Signal Transducing - metabolism; Biological Transport; Capsid - metabolism; Cell Line; Cell Nucleus - metabolism; Dyneins - metabolism; Fibroblasts; HEK293 Cells; HIV-1 - metabolism; Humanities and Social Sciences; Humans; Kinesin - metabolism; Microglia; Microtubules - metabolism; Monocytes; multidisciplinary; Nerve Tissue Proteins - metabolism; RNA Interference; Science; Science (multidisciplinary); T-Lymphocytes
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms7660

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.
Many viruses take advantage of microtubule-dependent motor proteins to move through the cell. Malikov
et al
. show that HIV-1 recruits the kinesin-1 adaptor FEZ1, and that the opposing activities of kinesin-1 and dynein motors are both required for the transport of HIV-1 capsids towards the nucleus.