HIV-1 capsids enter the FG phase of nuclear pores like a transport receptor

Fu, Liran and Weiskopf, Erika N. and Akkermans, Onno and Swanson, Nicholas A. and Cheng, Shiya and Schwartz, Thomas U. and Görlich, Dirk (2024) HIV-1 capsids enter the FG phase of nuclear pores like a transport receptor. Nature, 626 (8000). pp. 843-851. ISSN 0028-0836

[thumbnail of s41586-023-06966-w.pdf] Text
s41586-023-06966-w.pdf - Published Version

Download (20MB)

Abstract

HIV-1 infection requires nuclear entry of the viral genome. Previous evidence suggests that this entry proceeds through nuclear pore complexes (NPCs), with the 120 × 60 nm capsid squeezing through an approximately 60-nm-wide central channel1 and crossing the permeability barrier of the NPC. This barrier can be described as an FG phase2 that is assembled from cohesively interacting phenylalanine–glycine (FG) repeats3 and is selectively permeable to cargo captured by nuclear transport receptors (NTRs). Here we show that HIV-1 capsid assemblies can target NPCs efficiently in an NTR-independent manner and bind directly to several types of FG repeats, including barrier-forming cohesive repeats. Like NTRs, the capsid readily partitions into an in vitro assembled cohesive FG phase that can serve as an NPC mimic and excludes much smaller inert probes such as mCherry. Indeed, entry of the capsid protein into such an FG phase is greatly enhanced by capsid assembly, which also allows the encapsulated clients to enter. Thus, our data indicate that the HIV-1 capsid behaves like an NTR, with its interior serving as a cargo container. Because capsid-coating with trans-acting NTRs would increase the diameter by 10 nm or more, we suggest that such a ‘self-translocating’ capsid undermines the size restrictions imposed by the NPC scaffold, thereby bypassing an otherwise effective barrier to viral infection.

Item Type: Article
Subjects: Institute Archives > Multidisciplinary
Depositing User: Managing Editor
Date Deposited: 24 Feb 2024 06:36
Last Modified: 24 Feb 2024 06:36
URI: http://eprint.subtopublish.com/id/eprint/4116

Actions (login required)

View Item
View Item