The precise sequence of steps and partners involved in moving viruses and other macromolecular cargoes through the 30-protein nuclear pore complex (NPC) remains unclear. The human immunodeficiency virus type 1 (HIV-1) serves as a useful model to dissect this process, as this retrovirus displays considerable flexibility in its ability to access the nucleus to establish the proviral state.
In new work, Xue et al. extend previous findings by reporting that the HIV-1 capsid (CA) core functions as a nuclear transport receptor (NTR) that interacts with the nucleoporins (Nups) Nup35, Nup153, and POM121. Direct CA contact with Nup35 and POM121 is mediated by the phenylalanine glycine motifs (FG-motifs) in these Nups (1). Importantly, these interactions involve the soluble host factors Cyclophilin A (CypA) and CPSF6, which bind different regions of CA. The binding of CypA enhances HIV-1 CA interaction with the FG-motifs of Nup35, Nup153, and POM121, while CPSF6 interaction assists with NPC release of HIV-1. This study builds on earlier research by this group demonstrating how HIV-1 CA is the crucial viral component determining Nup engagement, with even single amino acid changes in CA resulting in differential Nup interaction (2). These combined data not only illuminate how HIV-1 completes the essential task of nuclear import, but also expands our knowledge of macromolecular movement across the nuclear membrane.
GeneTex’s antibody catalog includes reagents for membrane transport research, including the POM121 antibody [N2N3] (GTX102128) and Nup53 antibody (GTX64510) cited in the Xue et al. paper. For more details, please see the highlighted product images below and visit our website at www.genetex.com.
- Nat Commun. 2023 Jun 24;14(1):3782. doi: 10.1038/s41467-023-39146-5.
- Cell Host Microbe 7, 221–233 (2010).