HIV-1 induces the formation of stable microtubules to enhance early infection

Yosef Sabo, Derek Walsh, Denis S. Barry, Sedef Tinaztepe, Kenia De Los Santos, Stephen P. Goff, Gregg G. Gundersen, Mojgan H. Naghavi*

*Corresponding author for this work

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)535-546
Number of pages12
JournalCell Host and Microbe
Volume14
Issue number5
DOIs
StatePublished - Nov 13 2013

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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    Sabo, Y., Walsh, D., Barry, D. S., Tinaztepe, S., De Los Santos, K., Goff, S. P., Gundersen, G. G., & Naghavi, M. H. (2013). HIV-1 induces the formation of stable microtubules to enhance early infection. Cell Host and Microbe, 14(5), 535-546. https://doi.org/10.1016/j.chom.2013.10.012