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Author Notes:

Vineet N. KewalRamani, vineet@mail.nih.gov

G.X., F.D.G., J.L., and V.N.K. oversaw the design of the entire study. G.X. conducted and analyzed most experiments. H.J.Y. collected and analyzed the microscopic imaging data. C.B. performed CA-NC binding experiment. G.X., H.J.Y, S.W.H., C.B., F.D.G., A.T.G., S.G.S., and V.N.K. helped with Figures. J.L. suggested important experiments to examine the biological function of factors in supporting HIV-1 infection. S.G.S. provided insight on CA interactions with multiple host factors. S.W.H., K.L., S.L.G., and M.H.G. provided valuable discussions/technical expertise/guidance. J.L., F.D.G., and V.N.K. supervised the experiments. G.X. and V.N.K. wrote the manuscript with input from all authors.

The authors thank Eric Freed, Henry Levin, and Owen Pornillos for scientific suggestions, and Eric Freed for MT4 cells. We thank Joseph Meyer from Scientific Publications, Graphics and Media, Frederick National Laboratory for assistance with figure graphics. Dr. Xue was an NIH Intramural AIDS Research Fellow and an NCI Sallie Rosen Kaplan Award recipient for women scientists. This research was supported by the Intramural Research Program of the NCI, Frederick National Lab, Center for Cancer Research. This work was also supported by NIH grants 5R01AI111809, 5DP1DA034990, and 1R01AI117839, to J.L. S.G.S. acknowledges support by NIH grants P50 GM103368 and R01 AI120860. F.D.-G., C.B. and A.B.-R. were supported by an R01 grant from the NIH AI087390, to F.D.-G. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.

G.X. is an employee of AstraZeneca and has stock ownership and/or stock options or interests in the company. The remaining authors declare no competing interests.

Subjects:

Keywords:

  • Humans
  • Active Transport, Cell Nucleus
  • HIV-1
  • Capsid
  • Cell Line
  • Nuclear Pore Complex Proteins
  • Capsid Proteins
  • Nuclear Pore
  • Membrane Glycoproteins

The HIV-1 capsid core is an opportunistic nuclear import receptor

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Journal Title:

Nature Communications

Volume:

Volume 14, Number 1

Publisher:

, Pages 3782-3782

Type of Work:

Article | Final Publisher PDF

Abstract:

The movement of viruses and other large macromolecular cargo through nuclear pore complexes (NPCs) is poorly understood. The human immunodeficiency virus type 1 (HIV-1) provides an attractive model to interrogate this process. HIV-1 capsid (CA), the chief structural component of the viral core, is a critical determinant in nuclear transport of the virus. HIV-1 interactions with NPCs are dependent on CA, which makes direct contact with nucleoporins (Nups). Here we identify Nup35, Nup153, and POM121 to coordinately support HIV-1 nuclear entry. For Nup35 and POM121, this dependence was dependent cyclophilin A (CypA) interaction with CA. Mutation of CA or removal of soluble host factors changed the interaction with the NPC. Nup35 and POM121 make direct interactions with HIV-1 CA via regions containing phenylalanine glycine motifs (FG-motifs). Collectively, these findings provide additional evidence that the HIV-1 CA core functions as a macromolecular nuclear transport receptor (NTR) that exploits soluble host factors to modulate NPC requirements during nuclear invasion.

Copyright information:

© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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