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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2017,1,24]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Effective prevention strategies are urgently needed to control the spread of HIV-1. A critical barrier to developing such strategies is the lack of understanding of the host antiviral defenses that control HIV-1 replication in the mucosa at the site of entry. Here, we characterized viruses from matched donor and recipient pairs to determine whether transmitted HIV-1 strains exhibit traits that increase their transmission fitness. Characterizing 300 limiting dilution-derived isolates, we identified several properties that enhance virus replication in the face of a vigorous innate immune response, of which resistance to type 1 IFNs is the most important. These results provide new insights into the HIV-1 transmission process and define possible new targets for AIDS prevention and therapy.<\/jats:p>","DOI":"10.1073\/pnas.1620144114","type":"journal-article","created":{"date-parts":[[2017,1,9]],"date-time":"2017-01-09T22:00:32Z","timestamp":1483999232000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":141,"title":["Resistance to type 1 interferons is a major determinant of HIV-1 transmission fitness"],"prefix":"10.1073","volume":"114","author":[{"given":"Shilpa S.","family":"Iyer","sequence":"first","affiliation":[{"name":"Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;"},{"name":"Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"Bibollet-Ruche","sequence":"additional","affiliation":[{"name":"Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Sherrill-Mix","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald H.","family":"Learn","sequence":"additional","affiliation":[{"name":"Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey","family":"Plenderleith","sequence":"additional","affiliation":[{"name":"Institute of Evolutionary Biology, and Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh EH9 3FL, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew G.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah J.","family":"Barbian","sequence":"additional","affiliation":[{"name":"Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;"},{"name":"Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronnie M.","family":"Russell","sequence":"additional","affiliation":[{"name":"Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;"},{"name":"Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos V. P.","family":"Gondim","sequence":"additional","affiliation":[{"name":"Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine Y.","family":"Bahari","sequence":"additional","affiliation":[{"name":"Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiana M.","family":"Shaw","sequence":"additional","affiliation":[{"name":"Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Decker","sequence":"additional","affiliation":[{"name":"Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barton F.","family":"Haynes","sequence":"additional","affiliation":[{"name":"Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710;"},{"name":"Department of Medicine, Duke University Medical Center, Durham, NC 27710;"},{"name":"Department of Immunology, Duke University Medical Center, Durham, NC 27710;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George M.","family":"Shaw","sequence":"additional","affiliation":[{"name":"Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;"},{"name":"Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M.","family":"Sharp","sequence":"additional","affiliation":[{"name":"Institute of Evolutionary Biology, and Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh EH9 3FL, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Persephone","family":"Borrow","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7FZ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice H.","family":"Hahn","sequence":"additional","affiliation":[{"name":"Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;"},{"name":"Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2017,1,9]]},"reference":[{"key":"e_1_3_4_1_2","unstructured":"; UNAIDS Global AIDS Update 2016. 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Cell Host Microbe 19, 292\u2013303 (2016).","journal-title":"Cell Host Microbe"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/nri2302","article-title":"Setting the stage: Host invasion by HIV","volume":"8","author":"Hladik F","year":"2008","unstructured":"F Hladik, MJ McElrath, Setting the stage: Host invasion by HIV. Nat Rev Immunol 8, 447\u2013457 (2008).","journal-title":"Nat Rev Immunol"},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1182\/blood-2010-12-325860","article-title":"Barriers to mucosal transmission of immunodeficiency viruses","volume":"118","author":"Keele BF","year":"2011","unstructured":"BF Keele, JD Estes, Barriers to mucosal transmission of immunodeficiency viruses. 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PLoS Pathog 11, e1005154 (2015).","journal-title":"PLoS Pathog"},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s12977-016-0299-0","article-title":"Tracing HIV-1 transmission: Envelope traits of HIV-1 transmitter and recipient pairs","volume":"13","author":"Oberle CS","year":"2016","unstructured":"CS Oberle, , Tracing HIV-1 transmission: Envelope traits of HIV-1 transmitter and recipient pairs. Retrovirology; Swiss HIV Cohort Study 13, 62 (2016).","journal-title":"Retrovirology"},{"key":"e_1_3_4_29_2","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1038\/ni.3157","article-title":"Innate immunity against HIV-1 infection","volume":"16","author":"Altfeld M","year":"2015","unstructured":"M Altfeld, Jr M Gale, Innate immunity against HIV-1 infection. Nat Immunol 16, 554\u2013562 (2015).","journal-title":"Nat Immunol"},{"key":"e_1_3_4_30_2","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.immuni.2006.08.007","article-title":"Type I interferons in host defense","volume":"25","author":"Stetson DB","year":"2006","unstructured":"DB Stetson, R Medzhitov, Type I interferons in host defense. Immunity 25, 373\u2013381 (2006).","journal-title":"Immunity"},{"key":"e_1_3_4_31_2","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.coviro.2014.03.006","article-title":"Interferon-stimulated genes: Roles in viral pathogenesis","volume":"6","author":"Schoggins JW","year":"2014","unstructured":"JW Schoggins, Interferon-stimulated genes: Roles in viral pathogenesis. Curr Opin Virol 6, 40\u201346 (2014).","journal-title":"Curr Opin Virol"},{"key":"e_1_3_4_32_2","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/nrmicro3449","article-title":"HIV-1 and interferons: Who\u2019s interfering with whom?","volume":"13","author":"Doyle T","year":"2015","unstructured":"T Doyle, C Goujon, MH Malim, HIV-1 and interferons: Who\u2019s interfering with whom? Nat Rev Microbiol 13, 403\u2013413 (2015).","journal-title":"Nat Rev Microbiol"},{"key":"e_1_3_4_33_2","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.chom.2014.06.009","article-title":"Interactions between HIV-1 and the cell-autonomous innate immune system","volume":"16","author":"Towers GJ","year":"2014","unstructured":"GJ Towers, M Noursadeghi, Interactions between HIV-1 and the cell-autonomous innate immune system. Cell Host Microbe 16, 10\u201318 (2014).","journal-title":"Cell Host Microbe"},{"key":"e_1_3_4_34_2","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1038\/nature13554","article-title":"Type I interferon responses in rhesus macaques prevent SIV infection and slow disease progression","volume":"511","author":"Sandler NG","year":"2014","unstructured":"NG Sandler, , Type I interferon responses in rhesus macaques prevent SIV infection and slow disease progression. Nature 511, 601\u2013605 (2014).","journal-title":"Nature"},{"key":"e_1_3_4_35_2","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1038\/mi.2015.146","article-title":"Prevention of SHIV transmission by topical IFN-\u03b2 treatment","volume":"9","author":"Veazey RS","year":"2016","unstructured":"RS Veazey, , Prevention of SHIV transmission by topical IFN-\u03b2 treatment. Mucosal Immunol 9, 1528\u20131536 (2016).","journal-title":"Mucosal Immunol"},{"key":"e_1_3_4_36_2","doi-asserted-by":"crossref","first-page":"12164","DOI":"10.1128\/JVI.79.19.12164-12172.2005","article-title":"Temporal and anatomic relationship between virus replication and cytokine gene expression after vaginal simian immunodeficiency virus infection","volume":"79","author":"Abel K","year":"2005","unstructured":"K Abel, DM Rocke, B Chohan, L Fritts, CJ Miller, Temporal and anatomic relationship between virus replication and cytokine gene expression after vaginal simian immunodeficiency virus infection. 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