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bioRxiv · 10.1101/2021.12.02.470925

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

Xue, G.·Yu, H. J.·Goh, S. L.·Gres, A. T.·Guney, M. H.·Sarafianos, S. G.·Luban, J.·KewalRamani, V. N.
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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.

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Xue, G., Yu, H. J., Goh, S. L., Gres, A. T., Guney, M. H., Sarafianos, S. G., Luban, J., KewalRamani, V. N.. 2021-12-02. The HIV-1 capsid core is an opportunistic nuclear import receptor. https://doi.org/10.1101/2021.12.02.470925

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