HIV-1 uncoating is facilitated by dynein and kinesin 1

Zana Lukic, Adarsh Dharan, Thomas Fricke, Felipe Diaz-Griffero, Edward M. Campbell

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

Following entry into the target cell, human immunodeficiency virus type 1 (HIV-1) must reverse transcribe its RNA genome to DNA and traffic to the nuclear envelope, where the viral genome is translocated into the nucleus for subsequent integration into the host cell chromosome. During this time, the viral core, which houses the genome, undergoes a poorly understood process of disassembly, known as uncoating. Collectively, many studies suggest that uncoating is tightly regulated to allow nuclear import of the genome while minimizing the exposure of the newly synthesized DNA to cytosolic DNA sensors. However, whether host cellular proteins facilitate this process remains poorly understood. Here we report that intact microtubules facilitate HIV-1 uncoating in target cells. Disruption of microtubules with nocodazole substantially delays HIV-1 uncoating, as revealed with three different assay systems. This defect in uncoating did not correlate with defective reverse transcription at early times postinfection, demonstrating that microtubule-facilitated uncoating is distinct from the previously reported role of viral reverse transcription in the uncoating process. We also find that pharmacological or small interfering RNA (siRNA)-mediated inhibition of cytoplasmic dynein or the kinesin 1 heavy chain KIF5B delays uncoating, providing detailed insight into how microtubules facilitate the uncoating process. These studies reveal a previously unappreciated role for microtubules and microtubule motor function in HIV-1 uncoating, establishing a functional link between viral trafficking and uncoating. Targeted disruption of the capsid motor interaction may reveal novel mechanisms of inhibition of viral infection or provide opportunities to activate cytoplasmic antiviral responses directed against capsid or viral DNA.

Original languageEnglish (US)
Pages (from-to)13613-13625
Number of pages13
JournalJournal of virology
Volume88
Issue number23
DOIs
StatePublished - Jan 1 2014

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ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Lukic, Z., Dharan, A., Fricke, T., Diaz-Griffero, F., & Campbell, E. M. (2014). HIV-1 uncoating is facilitated by dynein and kinesin 1. Journal of virology, 88(23), 13613-13625. https://doi.org/10.1128/JVI.02219-14