UMass Chan Medical School Faculty Publications
UMMS Affiliation
Program in Molecular Medicine; Graduate School of Biomedical Sciences
Publication Date
2021-12-02
Document Type
Article Preprint
Disciplines
Cell Biology | Genetics and Genomics | Structural Biology | Viruses
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 due to the genetic and cell biological assays to score virus nuclear entry in living cells. Although initial studies of HIV-1 infection of nondividing cells focused on karyophilic virion proteins, subsequent work revealed the viral capsid (CA), the chief structural component of the pre-integration complex (PIC), to be a critical determinant in nuclear transport1. In support of this model, HIV-1 interactions with NPCs can be altered through CA mutation2, which makes direct contact with nucleoporins (Nups)3–5. Here we identify Nup35, Nup153, and POM121 to coordinately support HIV-1 nuclear entry. For Nup35 and POM121, this dependence was strongly dependent cyclophilin A (CypA) interaction with CA. Mutation of CA or removal of soluble host factors changed the interaction with the NPC. Collectively, these findings implicate the HIV-1 CA hexameric lattice that encapsulates the viral genome as a macromolecular nuclear transport receptor (NTR) that exploits soluble host factors to modulate NPC requirements during nuclear invasion.
Keywords
Cell Biology, HIV-1, nuclear pore complexes, viral transport, nuclear transport
Rights and Permissions
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
DOI of Published Version
10.1101/2021.12.02.470925
Source
bioRxiv 2021.12.02.470925; doi: https://doi.org/10.1101/2021.12.02.470925. Link to preprint on bioRxiv.
Journal/Book/Conference Title
bioRxiv
Repository Citation
Xue G, Yu HJ, University of Massachusetts Medical School, Gres AT, Guney MH, Sarafianos SG, Luban J, KewalRamani VN. (2021). The HIV-1 capsid core is an opportunistic nuclear import receptor [preprint]. UMass Chan Medical School Faculty Publications. https://doi.org/10.1101/2021.12.02.470925. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/2212
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Included in
Cell Biology Commons, Genetics and Genomics Commons, Structural Biology Commons, Viruses Commons
Comments
This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.