Bicaudal D2 facilitates the cytoplasmic trafficking and nuclear import of HIV-1 genomes during infection

Adarsh Dharan, Silvana Opp, Omar Abdel-Rahim, Sevnur Komurlu Keceli, Sabrina Imam, Felipe Diaz-Griffero, Edward M. Campbell

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Numerous viruses, including HIV-1, exploit the microtubule network to traffic toward the nucleus during infection. Although numerous studies have observed a role for the minus-end microtubule motor dynein in HIV-1 infection, the mechanism by which the viral core containing the viral genome associates with dynein and induces its perinuclear trafficking has remained unclear. Here, we report that the dynein adapter protein bicaudal D2 (BICD2) is able to interact with HIV-1 viral cores in target cells. We also observe that BICD2 can bind in vitro-assembled capsid tubes through its CC3 domain. We observe that BICD2 facilitates infection by promoting the trafficking of viral cores to the nucleus, thereby promoting nuclear entry of the viral genome and infection. Finally, we observe that depletion of BICD2 in the monocytic cell line THP-1 results in an induction of IFN-stimulated genes in these cells. Collectively, these results identify a microtubule adapter protein critical for trafficking of HIV-1 in the cytoplasm of target cells and evasion of innate sensing mechanisms in macrophages.

Original languageEnglish (US)
Pages (from-to)E10707-E10716
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number50
DOIs
StatePublished - Dec 12 2017

Fingerprint

Cell Nucleus Active Transport
Dyneins
HIV-1
Genome
Viral Genome
Infection
Microtubules
Microtubule Proteins
Capsid
Protein Transport
Virus Diseases
HIV Infections
Cytoplasm
Macrophages
Viruses
Cell Line
Genes
Proteins

Keywords

  • BICD2
  • Dynein
  • HIV-1
  • Microtubules
  • Trafficking

ASJC Scopus subject areas

  • General

Cite this

Bicaudal D2 facilitates the cytoplasmic trafficking and nuclear import of HIV-1 genomes during infection. / Dharan, Adarsh; Opp, Silvana; Abdel-Rahim, Omar; Keceli, Sevnur Komurlu; Imam, Sabrina; Diaz-Griffero, Felipe; Campbell, Edward M.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 114, No. 50, 12.12.2017, p. E10707-E10716.

Research output: Contribution to journalArticle

Dharan, Adarsh ; Opp, Silvana ; Abdel-Rahim, Omar ; Keceli, Sevnur Komurlu ; Imam, Sabrina ; Diaz-Griffero, Felipe ; Campbell, Edward M. / Bicaudal D2 facilitates the cytoplasmic trafficking and nuclear import of HIV-1 genomes during infection. In: Proceedings of the National Academy of Sciences of the United States of America. 2017 ; Vol. 114, No. 50. pp. E10707-E10716.
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