HIV-1 induces the formation of stable microtubules to enhance early infection.
Stable microtubule (MT) subsets form distinct networks from dynamic MTs and acquire distinguishing posttranslational modifications, notably detyrosination and acetylation. Acting as specialized tracks for vesicle and macromolecular transport, their formation is regulated by the end-binding protein EB1, which recruits proteins that stabilize MTs. We show that HIV-1 induces the formation of acetylated and detyrosinated stable MTs early in infection. Although the MT depolymerizing agent nocodazole affected dynamic MTs, HIV-1 particles localized to nocodazole-resistant stable MTs, and infection was minimally affected. EB1 depletion or expression of an EB1 carboxy-terminal fragment that acts as a dominant-negative inhibitor of MT stabilization prevented HIV-1-induced stable MT formation and suppressed early viral infection. Furthermore, we show that the HIV-1 matrix protein targets the EB1-binding protein Kif4 to induce MT stabilization. Our findings illustrate how specialized MT-binding proteins mediate MT stabilization by HIV-1 and the importance of stable MT subsets in viral infection.
Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University, New York, NY 10032, USA.
Yosef
Y
Sabo
Derek
D
Walsh
Denis S
DS
Barry
Sedef
S
Tinaztepe
Kenia
K
de Los Santos
Stephen P
SP
Goff
Gregg G
GG
Gundersen
Mojgan H
MH
Naghavi
D000107:Acetylation; D002460:Cell Line; D015488:HIV Antigens / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D016547:Kinesins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
D015488:HIV Antigens; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1; C484228:KIF4A protein, human; D016547:Kinesins