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

  1. Edward M. Campbella,c,1
  1. aDepartment of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153;
  2. bDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461;
  3. cInfectious Disease and Immunology Institute, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153
  1. Edited by John M. Coffin, Tufts University School of Medicine, Boston, MA, and approved November 7, 2017 (received for review July 7, 2017)

Significance

Following envelope-mediated fusion, the HIV-1 viral core, which houses the viral RNA and proteins required for virus reverse transcription and integration, must traffic toward the nucleus for subsequent nuclear import of the viral genome. In this study we examined the role of BICD2, a known dynein adaptor protein, for its role during the postentry trafficking of HIV-1 virions. We show that BICD2 binds viral capsid and mediates the postentry trafficking of HIV-1. Moreover, we also show that depletion of BICD2 sensitizes the virus to detection by innate immune sensing, revealing this BICD2 is necessary for the virus to avoid detection by innate sensing mechanisms in macrophages.

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.

Footnotes

  • ?1To whom correspondence should be addressed. Email: ecampbell{at}luc.edu.
  • Author contributions: A.D., S.O., S.K.K., S.I., F.D.-G., and E.M.C. designed research; A.D., S.O., O.A.-R., and S.I. performed research; F.D.-G. contributed new reagents/analytic tools; A.D., S.O., O.A.-R., S.K.K., F.D.-G., and E.M.C. analyzed data; and A.D. and E.M.C. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • This article contains supporting information online at www.danielhellerman.com/lookup/suppl/doi:10.1073/pnas.1712033114/-/DCSupplemental.

Published under the PNAS license.

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