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

Liran Fu, Erika N. Weiskopf, Onno Akkermans, Nicholas A. Swanson, Shiya Cheng, Thomas U. Schwartz () and Dirk Görlich ()
Additional contact information
Liran Fu: Max Planck Institute for Multidisciplinary Sciences
Erika N. Weiskopf: Massachusetts Institute of Technology
Onno Akkermans: Massachusetts Institute of Technology
Nicholas A. Swanson: Massachusetts Institute of Technology
Shiya Cheng: Max Planck Institute for Multidisciplinary Sciences
Thomas U. Schwartz: Massachusetts Institute of Technology
Dirk Görlich: Max Planck Institute for Multidisciplinary Sciences

Nature, 2024, vol. 626, issue 8000, 843-851

Abstract: 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.

Date: 2024
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41586-023-06966-w Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:626:y:2024:i:8000:d:10.1038_s41586-023-06966-w

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-023-06966-w

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().