{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T16:40:32Z","timestamp":1764175232012,"version":"3.40.5"},"reference-count":103,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T00:00:00Z","timestamp":1650844800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>In HIV-1-infected individuals, transmitted\/founder (TF) virus contributes to establish new infection and expands during the acute phase of infection, while chronic control (CC) virus emerges during the chronic phase of infection. TF viruses are more resistant to interferon-alpha (IFN-\u03b1)-mediated antiviral effects than CC virus, however, its virological relevance in infected individuals remains unclear. Here we perform an experimental-mathematical investigation and reveal that IFN-\u03b1 strongly inhibits cell-to-cell infection by CC virus but only weakly affects that by TF virus. Surprisingly, IFN-\u03b1 enhances cell-free infection of HIV-1, particularly that of CC virus, in a virus-cell density-dependent manner. We further demonstrate that LY6E, an IFN-stimulated gene, can contribute to the density-dependent enhancement of cell-free HIV-1 infection. Altogether, our findings suggest that the major difference between TF and CC viruses can be explained by their resistance to IFN-\u03b1-mediated inhibition of cell-to-cell infection and their sensitivity to IFN-\u03b1-mediated enhancement of cell-free infection.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1010053","type":"journal-article","created":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T17:24:44Z","timestamp":1650907484000},"page":"e1010053","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Antithetic effect of interferon-\u03b1 on cell-free and cell-to-cell HIV-1 infection"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6428-6357","authenticated-orcid":true,"given":"Ryuichi","family":"Kumata","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1474-5348","authenticated-orcid":true,"given":"Shoya","family":"Iwanami","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3640-2418","authenticated-orcid":true,"given":"Katrina B.","family":"Mar","sequence":"additional","affiliation":[]},{"given":"Yusuke","family":"Kakizoe","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9362-803X","authenticated-orcid":true,"given":"Naoko","family":"Misawa","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3277-9552","authenticated-orcid":true,"given":"Shinji","family":"Nakaoka","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3007-6642","authenticated-orcid":true,"given":"Yoshio","family":"Koyanagi","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2455-0002","authenticated-orcid":true,"given":"Alan S.","family":"Perelson","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7944-6800","authenticated-orcid":true,"given":"John W.","family":"Schoggins","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1780-350X","authenticated-orcid":true,"given":"Shingo","family":"Iwami","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4431-1380","authenticated-orcid":true,"given":"Kei","family":"Sato","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2022,4,25]]},"reference":[{"issue":"9263","key":"pcbi.1010053.ref001","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1016\/S0140-6736(00)04331-2","article-title":"Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1-discordant couples in Rakai, Uganda.","volume":"357","author":"RH Gray","year":"2001","journal-title":"Lancet"},{"issue":"6","key":"pcbi.1010053.ref002","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1084\/jem.20090378","article-title":"Genetic identity, biological phenotype, and evolutionary pathways of transmitted\/founder viruses in acute and early HIV-1 infection","volume":"206","author":"JF Salazar-Gonzalez","year":"2009","journal-title":"J Exp Med"},{"issue":"18","key":"pcbi.1010053.ref003","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1056\/NEJMoa042291","article-title":"Detection of acute infections during HIV testing in North Carolina","volume":"352","author":"CD Pilcher","year":"2005","journal-title":"N Engl J Med"},{"issue":"5","key":"pcbi.1010053.ref004","doi-asserted-by":"crossref","first-page":"e1004092","DOI":"10.1371\/journal.ppat.1004092","article-title":"Cellular superspreaders: an epidemiological perspective on HIV infection inside the body.","volume":"10","author":"K Talbert-Slagle","year":"2014","journal-title":"PLoS Pathog."},{"issue":"4","key":"pcbi.1010053.ref005","first-page":"E590","article-title":"Resistance to type 1 interferons is a major determinant of HIV-1 transmission fitness","volume":"114","author":"SS Iyer","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"17","key":"pcbi.1010053.ref006","doi-asserted-by":"crossref","first-page":"6626","DOI":"10.1073\/pnas.1304288110","article-title":"Phenotypic properties of transmitted founder HIV-1","volume":"110","author":"NF Parrish","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6193","key":"pcbi.1010053.ref007","doi-asserted-by":"crossref","first-page":"1254031","DOI":"10.1126\/science.1254031","article-title":"HIV transmission. 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