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

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 associate...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2017-12, Vol.114 (50), p.E10707-E10716
Main Authors: Dharan, Adarsh, Opp, Silvana, Abdel-Rahim, Omar, Keceli, Sevnur Komurlu, Imam, Sabrina, Diaz-Griffero, Felipe, Campbell, Edward M.
Format: Article
Language:English
Subjects:
Active Transport, Cell Nucleus
Biological Sciences
Capsid - metabolism
Cell Nucleus - virology
Cells
Cytoplasm
Cytoplasm - virology
Gene Knockout Techniques
Genes
Genome, Viral
Genomes
HEK293 Cells
HeLa Cells
HIV
HIV Infections - metabolism
HIV Infections - virology
HIV-1 - genetics
HIV-1 - immunology
HIV-1 - metabolism
Human immunodeficiency virus
Humans
Macrophages - immunology
Microtubule-Associated Proteins - genetics
Microtubule-Associated Proteins - metabolism
PNAS Plus
Virus Internalization
Virus Replication
Virus Uncoating
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1712033114