HIV-1 Induces the Formation of Stable Microtubules to Enhance Early Infection

• Published in: Cell host & microbe Vol. 14; no. 5; pp. 535 - 546
• Main Authors: Sabo, Yosef, Walsh, Derek, Barry, Denis S., Tinaztepe, Sedef, de los Santos, Kenia, Goff, Stephen P., Gundersen, Gregg G., Naghavi, Mojgan H.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 13-11-2013
• Subjects: Acetylation; Cell Line; gag Gene Products, Human Immunodeficiency Virus - metabolism; HIV Antigens - metabolism; HIV-1 - physiology; Host-Pathogen Interactions; Humans; Kinesins - metabolism; Microtubules - metabolism; Protein Binding; Protein Processing, Post-Translational
• ISSN: 1931-3128; 1934-6069
• DOI: 10.1016/j.chom.2013.10.012

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.
•HIV-1 induces microtubule (MT) stabilization to facilitate early infection•EB1 is a critical host regulator of MT stabilization and viral infection•Kif4 binds EB1 and mediates MT stabilization by the HIV-1 matrix protein