Dataset Information

Transportin-1 (TRN-1) orchestrates HIV-1 uncoating and nuclear import

ABSTRACT: Timely uncoating and nuclear import are key to efficient HIV infection, however the triggers and mechanisms that orchestrate these steps are unknown. Here we show that HIV-1 exploits Transportin-1/TRN-1 for both uncoating and nuclear import. Depletion of TRN-1, which we characterised by mass spectrometry, significantly reduced the early steps of HIV-1 infection in cell lines and primary CD4+ T cells. We showed that TRN-1 binds to incoming HIV-1 capsid (CA) cores, but not monomeric CA or integrase, via a NLS present on the cyclophilin A (CypA) binding loop. The G89V mutant, but not P90A, relieved dependency on TRN-1, and TRN-1 binding to CA at position G89 displaced CypA, which likely contributes to weakening the CA assembly. Recombinant TRN-1 could induce CA uncoating in vitro indicating that disruption is entirely mechanical, and activity mapped to residue W730 that plays a pivotal role in binding to substrate NLS. HIV-1 intercepts TRN-1 near the nuclear envelope and complexes that fail to do so scatter back into the cytoplasm without uncoating. For complexes that uncoat, TRN-1 mediates the concomitant nuclear import of CA and viral DNA. Our study reveals how HIV-1 uses a single cellular protein to orchestrate the key steps that allow it to reach its replication compartment efficiently.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell

DISEASE(S): Human Immunodeficiency Virus Infectious Disease

SUBMITTER: Thibaut LEGER

LAB HEAD: Nathalie Arhel

PROVIDER: PXD010023 | Pride | 2019-09-25

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	15449001-QUANTI-peptide-measurements-3groups.xlsx	Xlsx
	15449001-QUANTI-peptide-measurements-shImpB1-EC.xlsx	Xlsx
	15449001-QUANTI-peptide-measurements-shTRN1-EC.xlsx	Xlsx
	15449001-QUANTI-peptide-measurements-shTRN1-shImpB1.xlsx	Xlsx
	15449001-QUANTI-protein-measurements-3groups.xlsx	Xlsx

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Publications

Transportin-1 binds to the HIV-1 capsid via a nuclear localization signal and triggers uncoating.

Fernandez Juliette J Machado Anthony K AK Lyonnais Sébastien S Chamontin Célia C Gärtner Kathleen K Léger Thibaut T Henriquet Corinne C Garcia Camille C Portilho Débora M DM Pugnière Martine M Chaloin Laurent L Muriaux Delphine D Yamauchi Yohei Y Blaise Mickaël M Nisole Sébastien S Arhel Nathalie J NJ

Nature microbiology 20191014 11

The initial steps of HIV replication in host cells prime the virus for passage through the nuclear pore and drive the establishment of a productive and irreparable infection1,2. The timely release of the viral genome from the capsid-referred to as uncoating-is emerging as a critical parameter for nuclear import, but the triggers and mechanisms that orchestrate these steps are unknown. Here, we identify β-karyopherin Transportin-1 (TRN-1) as a cellular co-factor o ...[more]

PMID: 31611641

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