{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:42:29Z","timestamp":1792024949788,"version":"4.4.0"},"reference-count":60,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2025,11,25]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">N<\/jats:italic>\n                      <jats:sup>6<\/jats:sup>\n                      -methyladenosine (m\n                      <jats:sup>6<\/jats:sup>\n                      A) plays a critical role in regulating RNA Ostability, localization, and gene expression. m\n                      <jats:sup>6<\/jats:sup>\n                      A modification is also important for modulating the expression of viral and cellular genes during HIV-1 infection. However, the function of m\n                      <jats:sup>6<\/jats:sup>\n                      A modification in regulating HIV-1 infection of primary CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells remains unclear. Here, we demonstrate that HIV-1 infection of activated primary CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells promotes the interaction between the m\n                      <jats:sup>6<\/jats:sup>\n                      A writer complex subunits methyltransferase-like 3 and 14 (METTL3\/METTL14). Using single-base m\n                      <jats:sup>6<\/jats:sup>\n                      A-specific RNA sequencing, we identified differentially m\n                      <jats:sup>6<\/jats:sup>\n                      A-modified cellular mRNAs in HIV-1-infected primary CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells, including\n                      <jats:italic toggle=\"yes\">perilipin 3<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">PLIN3<\/jats:italic>\n                      ). We also identified 30 m\n                      <jats:sup>6<\/jats:sup>\n                      A sites in HIV-1 RNA from infected primary CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells. HIV-1 infection increased\n                      <jats:italic toggle=\"yes\">PLIN3<\/jats:italic>\n                      mRNA level and nuclear accumulation but decreased PLIN3 protein expression in primary CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells. Polysome profiling revealed that\n                      <jats:italic toggle=\"yes\">PLIN3<\/jats:italic>\n                      mRNA was less actively translated during HIV-1 infection of primary CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells. Furthermore, PLIN3 knockdown in primary CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells significantly reduced HIV-1 release but enhanced virion infectivity. Our results highlight the importance of m\n                      <jats:sup>6<\/jats:sup>\n                      A RNA modification during HIV-1 infection and suggest PLIN3 as a regulatory protein of HIV-1 replication in primary CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        m\n                        <jats:sup>6<\/jats:sup>\n                        A is a common chemical modification on mRNA that regulates RNA stability, localization, and gene expression. m\n                        <jats:sup>6<\/jats:sup>\n                        A modification of viral and cellular RNA is important for HIV-1 infection. We found that HIV-1 infection of primary CD4\n                        <jats:sup>+<\/jats:sup>\n                        T cells promotes the interaction between the m\n                        <jats:sup>6<\/jats:sup>\n                        A writer complex subunits that add m\n                        <jats:sup>6<\/jats:sup>\n                        A modification. Using m\n                        <jats:sup>6<\/jats:sup>\n                        A-specific RNA sequencing, we identified several cellular mRNAs with altered m\n                        <jats:sup>6<\/jats:sup>\n                        A modifications during HIV-1 infection, including\n                        <jats:italic toggle=\"yes\">PLIN3<\/jats:italic>\n                        . Interestingly, HIV-1 infection increased\n                        <jats:italic toggle=\"yes\">PLIN3<\/jats:italic>\n                        mRNA levels and nuclear localization but reduced PLIN3 protein expression in primary CD4\n                        <jats:sup>+<\/jats:sup>\n                        T cells. When we knocked down PLIN3 in primary CD4\n                        <jats:sup>+<\/jats:sup>\n                        T cells, it decreased HIV-1 release but made the HIV-1 more infectious. Our findings show the importance of m\n                        <jats:sup>6<\/jats:sup>\n                        A RNA modification in HIV-1 infection by regulating host genes like\n                        <jats:italic toggle=\"yes\">PLIN3<\/jats:italic>\n                        and suggest a unique regulatory mechanism in HIV-1-infected primary CD4\n                        <jats:sup>+<\/jats:sup>\n                        T cells.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.01536-25","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T13:10:15Z","timestamp":1760447415000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["Single-base m\n                    <sup>6<\/sup>\n                    A epitranscriptomics reveals novel HIV-1 host interaction targets in primary CD4\n                    <sup>+<\/sup>\n                    T cells"],"prefix":"10.1128","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-6107-6911","authenticated-orcid":false,"given":"Siyu","family":"Huang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036jqmy94","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Carver College of Medicine, The University of Iowa","place":["Iowa City, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4496-1394","authenticated-orcid":true,"given":"Yutao","family":"Zhao","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/024mw5h28","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, Institute for Biophysical Dynamics, University of Chicago","place":["Chicago, USA"]},{"id":[{"id":"https:\/\/ror.org\/024mw5h28","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular 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