{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:35:36Z","timestamp":1792035336220,"version":"4.4.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009421","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T00:00:00Z","timestamp":1616371200000}}],"reference-count":65,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T00:00:00Z","timestamp":1615334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI150343"],"award-info":[{"award-number":["R01AI150343"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI141495"],"award-info":[{"award-number":["R01AI141495"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 ES030546"],"award-info":[{"award-number":["R01 ES030546"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    <jats:italic>N<\/jats:italic>\n                    <jats:sup>6<\/jats:sup>\n                    -methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A) is a prevalent RNA modification that plays a key role in regulating eukaryotic cellular mRNA functions. RNA m\n                    <jats:sup>6<\/jats:sup>\n                    A modification is regulated by two groups of cellular proteins, writers and erasers that add or remove m\n                    <jats:sup>6<\/jats:sup>\n                    A, respectively. HIV-1 RNA contains m\n                    <jats:sup>6<\/jats:sup>\n                    A modifications that modulate viral infection and gene expression in CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells. However, it remains unclear whether m\n                    <jats:sup>6<\/jats:sup>\n                    A modifications of HIV-1 RNA modulate innate immune responses in myeloid cells that are important for antiviral immunity. Here we show that m\n                    <jats:sup>6<\/jats:sup>\n                    A modification of HIV-1 RNA suppresses the expression of antiviral cytokine type-I interferon (IFN-I) in differentiated human monocytic cells and primary monocyte-derived macrophages. Transfection of differentiated monocytic U937 cells with HIV-1 RNA fragments containing a single m\n                    <jats:sup>6<\/jats:sup>\n                    A-modification significantly reduced IFN-I mRNA expression relative to their unmodified RNA counterparts. We generated HIV-1 with altered m\n                    <jats:sup>6<\/jats:sup>\n                    A levels of RNA by manipulating the expression of the m\n                    <jats:sup>6<\/jats:sup>\n                    A erasers (FTO and ALKBH5) or pharmacological inhibition of m\n                    <jats:sup>6<\/jats:sup>\n                    A addition in virus-producing cells, or by treating HIV-1 RNA with recombinant FTO\n                    <jats:italic>in vitro<\/jats:italic>\n                    . HIV-1 RNA transfection or viral infection of differentiated U937 cells and primary macrophages demonstrated that HIV-1 RNA with decreased m\n                    <jats:sup>6<\/jats:sup>\n                    A levels enhanced IFN-I expression, whereas HIV-1 RNA with increased m\n                    <jats:sup>6<\/jats:sup>\n                    A modifications had opposite effects. Our mechanistic studies indicated that m\n                    <jats:sup>6<\/jats:sup>\n                    A of HIV-1 RNA escaped retinoic acid-induced gene I (RIG-I)-mediated RNA sensing and activation of the transcription factors IRF3 and IRF7 that drive IFN-I gene expression. Together, these findings suggest that m\n                    <jats:sup>6<\/jats:sup>\n                    A modifications of HIV-1 RNA evade innate immune sensing in myeloid cells.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1009421","type":"journal-article","created":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T13:47:28Z","timestamp":1615384048000},"page":"e1009421","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":94,"title":["N6-methyladenosine modification of HIV-1 RNA suppresses type-I interferon induction in differentiated monocytic cells and primary macrophages"],"prefix":"10.1371","volume":"17","author":[{"given":"Shuliang","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sameer","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7487-5254","authenticated-orcid":true,"given":"Constanza E.","family":"Espada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9042-5210","authenticated-orcid":true,"given":"Nagaraja","family":"Tirumuru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Cahill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7246-1736","authenticated-orcid":true,"given":"Lulu","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5468-2487","authenticated-orcid":true,"given":"Li","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,3,10]]},"reference":[{"issue":"7","key":"ppat.1009421.ref001","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1016\/j.cell.2017.05.045","article-title":"Dynamic RNA Modifications in Gene Expression Regulation","volume":"169","author":"IA 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