{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:33:34Z","timestamp":1785407614413,"version":"3.56.0"},"reference-count":51,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"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":[[2025,12,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Long-term non-progressors (LTNPs) represent a valuable model to investigate immunological features associated with non-progression in chronic HIV infection. In this study, single-cell RNA sequencing was performed on peripheral blood mononuclear cells obtained from 12 individuals, including 4 LTNPs, 4 typical progressors (TPs), and 4 healthy donors (HDs). Compared with TPs, LTNPs exhibited a higher percentage of naive T cells, whereas TPs showed a higher percentage of CD8\n                      <jats:sup>+<\/jats:sup>\n                      Effector-GNLY cells. LTNPs also exhibited lower gene-expression scores related to T-cell activation, cytotoxicity, inflammation, and interferon-alpha response across multiple effector-state T-cell subsets. GO enrichment analysis showed that compared with HDs and TPs, LTNPs exhibited downregulation of migration, translation, and antiviral response pathways in both CD4\n                      <jats:sup>+<\/jats:sup>\n                      and CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, with upregulation of stress\/inflammatory response and differentiation programs in CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells and of immune differentiation\/activation pathways in CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells. High-dimensional weighted gene co-expression network analysis (hdWGCNA) further revealed higher module eigengene expression of innate and myeloid-related modules and lower expression of B-cell and cytotoxicity-related modules in LTNPs compared with TPs. Additionally, HIV-1 RNA\n                      <jats:sup>+<\/jats:sup>\n                      cells were detected more frequently in TPs than in LTNPs and predominantly identified within CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells. Together, these findings reveal a transcriptionally balanced and favorable immunological profile associated with non-progressive HIV infection and inform the design of immune-based strategies toward a functional HIV cure.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Understanding molecular traits associated with natural control in LTNPs is critical for advancing HIV remission and cure strategies. Using single-cell RNA sequencing, we found that LTNPs had more naive T cells and fewer CD8\n                        <jats:sup>+<\/jats:sup>\n                        effector-GNLY cells than typical progressors, along with lower activation, cytotoxicity, inflammation, and IFN-\u03b1 scores across effector-state T-cell subsets. Differential expression and GO analyses showed predominant downregulation of migration, translation, and antiviral pathways, while preserving early activation markers. Co-expression network analysis revealed higher innate\/immune-regulatory module activity and lower B-cell and cytotoxicity modules in LTNPs. HIV-1 RNA\n                        <jats:sup>+<\/jats:sup>\n                        cells were detected less frequently in LTNPs and mainly detected in CD4\n                        <jats:sup>+<\/jats:sup>\n                        T cells. These findings highlight balanced immune programs in LTNPs, which may inform strategies toward a functional HIV cure.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.01597-25","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T13:00:56Z","timestamp":1763989256000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Single-cell transcriptome profiling reveals immunological fitness of HIV long-term non-progressors"],"prefix":"10.1128","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4150-925X","authenticated-orcid":false,"given":"Minjuan","family":"Shi","sequence":"first","affiliation":[{"name":"School of Public Health (Shenzhen), Sun Yat-Sen University","place":["Shenzhen, China"]},{"id":[{"id":"https:\/\/ror.org\/03dveyr97","id-type":"ROR","asserted-by":"publisher"}],"name":"Guangxi 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