{"doi":"10.1099/jgv.0.002104","title":"The identification of a novel interaction site for the human immunodeficiency virus capsid on nucleoporin 153","abstract":"Human immunodeficiency virus type-1 (HIV-1) can infect non-dividing cells by passing through the selective permeability barrier of the nuclear pore complex. The viral capsid is essential for successfully delivering the HIV-1 genome into the nucleus. Nucleoporin 153 (NUP153) interacts with the HIV-1 capsid via a C-terminal capsid-binding motif (hereafter named CbM.1) to licence HIV-1 nuclear ingress. Deletion or mutation of CbM.1 in NUP153 causes a reduction in capsid interaction but does not prevent HIV-1 nuclear ingress or completely block capsid interaction. This paper combines molecular modelling with biochemical and HIV infection assays to identify capsid-binding motif 2 (CbM.2) in the C-terminus of NUP153 that is similar in sequence to CbM.1. CbM.2 has an FG dipeptide motif predicted to interact with a hydrophobic pocket in capsid protein (CA) hexamers similar to CbM.1. CA hexamers can interact with CbM.2, and the deletion of both CbM.1 and CbM.2 results in a lower capsid interaction than a single CbM.1 deletion. The loss of CbM.1 is complemented by CbM.2, an interaction dependent on the FG motif. In the context of the nuclear pore complex, a loss-of-function mutation in CbM.1 reduces HIV nuclear ingress as measured by transduction and 2-LTR circles, whereas the mutation of CbM.2 causes a large increase in 2-LTR circles. Our results highlighted a previously unidentified FG dipeptide-containing motif (CbM.2) in NUP153 that binds the HIV-1 capsid at the common hydrophobic pocket on CA hexamers.","journal":"Journal of General Virology","year":2025,"id":565922,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9592,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":807448,"name":"Peik K. Lund-Andersen","orcid":null,"position":1,"is_corresponding":false},{"id":1117079,"name":"Szu‐Huan Wang","orcid":"0009-0009-8499-7066","position":2,"is_corresponding":false},{"id":371517,"name":"F. Marty Ytreberg","orcid":"0000-0001-7439-8224","position":3,"is_corresponding":false},{"id":303970,"name":"Mandar T. Naik","orcid":"0000-0002-7016-572X","position":4,"is_corresponding":false},{"id":371516,"name":"Jagdish Suresh Patel","orcid":"0000-0003-4999-5347","position":5,"is_corresponding":false},{"id":424085,"name":"Paul A. Rowley","orcid":"0000-0002-3590-5139","position":6,"is_corresponding":false},{"id":584824,"name":"Shunji Li","orcid":"0000-0003-1695-4899","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T02:56:32.546082Z","pmid":"40366356","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}