{"doi":"10.1073/pnas.2417676122","title":"Macropinosomes are a site of HIV-1 entry into primary CD4 <sup>+</sup> T cells","abstract":"HIV-1 has been observed to enter target cells at both the plasma membrane and endosomes. However, which pathways mediate its entry into primary CD4 + T cells, the major targets of this virus, remains unclear. Here, we show that HIV-1 can enter primary CD4 + T cells through macropinocytosis, a form of endocytosis. We found that HIV-1 can enter primary CD4 + T cells at both the plasma membrane and internal compartments, while entry into common T cell lines occurred primarily at the plasma membrane. Inhibition of macropinocytosis suppressed HIV-1 internalization into and subsequent fusion with primary CD4 + T cells regardless of the viral coreceptor usage. Microscopic analysis of viral contents exposed to the cytosol confirmed that HIV-1 fusion occurs at the macropinosomal membrane. Finally, the inhibition of macropinocytosis blocked HIV-1 infection of primary CD4 + T cells. Altogether, this study identifies macropinocytosis as one pathway for HIV-1 entry into primary CD4 + T cells.","journal":"Proceedings of the National Academy of Sciences","year":2025,"id":533834,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9524,"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":858071,"name":"Ricardo de Souza Cardoso","orcid":"0000-0003-2858-2076","position":1,"is_corresponding":false},{"id":562170,"name":"Praveen Manivannan","orcid":"0000-0002-2679-8626","position":2,"is_corresponding":false},{"id":1121791,"name":"Ya-Ting Chang","orcid":"0000-0002-1387-3076","position":3,"is_corresponding":false},{"id":714671,"name":"Eric C. Rentchler","orcid":null,"position":4,"is_corresponding":false},{"id":1416467,"name":"Kai-Neng Chou","orcid":null,"position":5,"is_corresponding":false},{"id":1243428,"name":"Yipei Tang","orcid":"0009-0007-7902-6316","position":6,"is_corresponding":false},{"id":301030,"name":"Joel A. Swanson","orcid":"0000-0003-0900-8212","position":7,"is_corresponding":false},{"id":301031,"name":"Philip D. King","orcid":"0000-0002-5598-2748","position":8,"is_corresponding":false},{"id":297876,"name":"Akira Ono","orcid":"0000-0001-7841-851X","position":9,"is_corresponding":false},{"id":747005,"name":"Tomoyuki Murakami","orcid":"0000-0002-6645-2240","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-19T02:51:43.451278Z","pmid":"40465625","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":[]}