Xue, GuangaiYu, Hyun JaeUniversity of Massachusetts Medical SchoolGres, Anna T.Guney, Mehmet HakanSarafianos, Stefan G.Luban, JeremyKewalRamani, Vineet N.2022-08-232022-08-232021-12-022022-06-02<p>bioRxiv 2021.12.02.470925; doi: https://doi.org/10.1101/2021.12.02.470925. <a href="https://doi.org/10.1101/2021.12.02.470925" target="_blank" title="view preprint in bioRxiv">Link to preprint on bioRxiv.</a></p>10.1101/2021.12.02.470925https://hdl.handle.net/20.500.14038/30741<p>This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.</p>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.en-USThe 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.http://creativecommons.org/licenses/by/4.0/Cell BiologyHIV-1nuclear pore complexesviral transportnuclear transportCell BiologyGenetics and GenomicsStructural BiologyVirusesPreprinthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3246&amp;context=faculty_pubs&amp;unstamped=1https://escholarship.umassmed.edu/faculty_pubs/221229508842faculty_pubs/2212