{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:20:33Z","timestamp":1792650033399,"version":"4.5.0"},"reference-count":58,"publisher":"National Academy of Sciences","issue":"23","license":[{"start":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T00:00:00Z","timestamp":1748995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI165381"],"award-info":[{"award-number":["R01 AI165381"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,6,10]]},"abstract":"<jats:p>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    T cells, the major targets of this virus, remains unclear. Here, we show that HIV-1 can enter primary CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells through macropinocytosis, a form of endocytosis. We found that HIV-1 can enter primary CD4\n                    <jats:sup>+<\/jats:sup>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Altogether, this study identifies macropinocytosis as one pathway for HIV-1 entry into primary CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2417676122","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T13:34:46Z","timestamp":1749044086000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":5,"title":["Macropinosomes are a site of HIV-1 entry into primary CD4\n                    <sup>+<\/sup>\n                    T cells"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6645-2240","authenticated-orcid":false,"given":"Tomoyuki","family":"Murakami","sequence":"first","affiliation":[{"name":"Department of Microbiology & Immunology, University of Michigan Medical School","place":["Ann Arbor"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo de Souza","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, University of Michigan Medical School","place":["Ann Arbor"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Praveen","family":"Manivannan","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, University of Michigan Medical School","place":["Ann Arbor"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1387-3076","authenticated-orcid":false,"given":"Ya-Ting","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, University of Michigan Medical School","place":["Ann Arbor"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Rentchler","sequence":"additional","affiliation":[{"name":"Microscopy core, Biomedical Research Core Facilities, Office of Research, University of Michigan Medical 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