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While most ISGs are antiviral, some ISGs have been shown to promote viral infection, including HIV-1 infection. We previously showed that IFN-inducible LY6E protein promotes HIV-1 infection in human PMBCs and high-CD4-expressing SupT1 cells. Here we found that LY6E inhibits HIV-1 entry and replication in low-CD4-expressing MDMs and Jurkat cells. Mechanistically, we demonstrated that LY6E downregulates the cell surface receptor CD4, thus impairing the virus binding to target cells. This is in contrast to the situation of high-CD4-expressing cells, where LY6E predominantly promotes viral membrane fusion. The opposing role of IFN-inducible LY6E in modulating HIV-1 infection highlights the complex roles of ISGs in viral infection and viral pathogenesis.<\/jats:p>","DOI":"10.1128\/jvi.01866-18","type":"journal-article","created":{"date-parts":[[2019,1,23]],"date-time":"2019-01-23T11:01:43Z","timestamp":1548241303000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":32,"title":["CD4-Dependent Modulation of HIV-1 Entry by LY6E"],"prefix":"10.1128","volume":"93","author":[{"given":"Jingyou","family":"Yu","sequence":"first","affiliation":[{"name":"Center for Retrovirus Research, The Ohio State University, Columbus, Ohio, USA"},{"name":"Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Liang","sequence":"additional","affiliation":[{"name":"McGill AIDS Centre, Lady Davis Institute, Montreal, Quebec, Canada"},{"name":"Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan-Lu","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Retrovirus Research, The Ohio State University, Columbus, Ohio, USA"},{"name":"Viruses and Emerging Pathogens Program, Infectious Diseases Institute, The Ohio State University, Columbus, Ohio, USA"},{"name":"Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USA"},{"name":"Department of Microbial Infection and Immunity, The Ohio State University, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61809-7"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006866"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-5-111"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/312763a0"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5371.1884"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.2174\/1570162043485086"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/350508a0"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/345625a0"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.66.1.226-234.1992"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1995.0035"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.08.055"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0156739"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01531-10"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature15399"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature15400"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3956"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-10-111"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.777714"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2014.11.001"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12977-014-0103-y"},{"key":"e_1_3_2_22_2","doi-asserted-by":"crossref","first-page":"2006","DOI":"10.4049\/jimmunol.148.7.2006","article-title":"Thymic shared antigen-1. 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