{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:45:03Z","timestamp":1785433503578,"version":"3.56.0"},"reference-count":51,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"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":["mBio"],"published-print":{"date-parts":[[2025,11,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Approximately 10\u201340% of patients with acquired immune deficiency syndrome (AIDS) fail to restore the number of CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells after antiretroviral therapy (ART). They are referred to as immunological non-responders (INRs) and have increased morbidity and mortality of AIDS and non-AIDS events. Pyroptosis is one of the key factors driving CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cell death in human immunodeficiency virus (HIV) infection, but its relationship with immune reconstitution and the underlying mechanisms is poorly understood. Through our\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      experiments, we showed that the expression of enolase 2 (ENO2) decreased in INRs and inhibited ENO2-enhanced CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cell pyroptosis through the regulation of reactive oxygen species (ROS). Furthermore, we discovered that supplementation with phosphoenolpyruvate (PEP), the catalytic product of ENO2, could restore mitochondrial function and reduce the pyroptosis of CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells. Our study clarified the ENO2-PEP-ROS-pyroptosis axis of CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells in INRs and provided a novel therapeutic target for enhancing immune reconstitution in HIV infection.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        The decrease in CD4\n                        <jats:sup>+<\/jats:sup>\n                        T cell count is an important cause of poor immune reconstitution in HIV-infected patients. In this study, we analyzed the pyroptosis of T cells in HIV-infected patients with poor immune reestablishment and demonstrated how ENO2, a key enzyme in the glycolytic pathway, affects pyroptosis through mitochondrial ROS. Our results clarified the role of ENO2 in regulating CD4\n                        <jats:sup>+<\/jats:sup>\n                        T cell pyroptosis in INRs and discussed its possible mechanism. This provides a new target for improving immune reconstitution and intervention in HIV infection.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.01702-25","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T13:23:56Z","timestamp":1758806636000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["ENO2 regulates CD4\n                    <sup>+<\/sup>\n                    T cell pyroptosis via mitochondrial ROS to drive immunological non-response in HIV infection"],"prefix":"10.1128","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6029-0810","authenticated-orcid":false,"given":"Siyao","family":"Li","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00v408z34","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory for Diagnosis and Treatment of Infectious 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