{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T19:39:20Z","timestamp":1793129960036,"version":"4.5.0"},"reference-count":64,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32370163"],"award-info":[{"award-number":["32370163"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2026,9,22]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Adverse pregnancy outcomes associated with dengue virus (DENV) infection are a severe manifestation of dengue fever; however, we still poorly understand the underlying mechanisms. Trophoblast dysfunction in the placenta contributes centrally to various pregnancy complications. As the functional unit of the placenta, the syncytiotrophoblast (STB) requires continuous fusion of precursor trophoblasts and adequate energy supply. In this study, we established a model of adverse pregnancy by infecting\n                      <jats:italic toggle=\"yes\">Ifnar<\/jats:italic>\n                      1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      pregnant mice with DENV-2. We did not detect viral replication within the placental trophoblast layer but observed substantial structural damage to the STB. RNA-seq analysis demonstrated that precursor trophoblasts exhibit disrupted glucose metabolism, and placental tissue upregulates pro-fusion genes\u2014yet fails to complete syncytialization. Metabolic assays revealed reduced ATP levels and elevated lactate concentrations, indicating that an inadequate energy supply impedes trophoblast differentiation. Treatment with the glycolytic inhibitor 2-DG restored oxidative phosphorylation (OXPHOS) activity in the placenta and markedly improved pathological outcomes. Further mechanistic studies established that DENV infection induces oxidative stress, which activates hypoxia-inducible factor Hif1\u03b1, leading to subsequent upregulation of lactate dehydrogenase (LDHA) expression. We identify this cascade as a fundamental mechanism underlying metabolic reprogramming in trophoblasts. Our findings not only clarify the key pathological processes driving DENV-induced adverse pregnancy outcomes but also propose novel therapeutic strategies for clinical intervention.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Dengue virus infection during pregnancy is linked to adverse fetal outcomes, but the underlying mechanisms remain unclear. In\n                        <jats:italic toggle=\"yes\">Ifnar<\/jats:italic>\n                        1\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                        pregnant mice, we show that fetal growth restriction is driven by disruption of the maternal environment that impairs placental function. We identify syncytiotrophoblast damage and defective trophoblast fusion despite compensatory upregulation of pro-fusion genes. Placental metabolic analysis reveals a shift from oxidative phosphorylation to glycolysis, accompanied by reduced ATP production and impaired syncytialization. Inhibition of glycolysis\n                        <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                        partially restores placental structure and improves fetal outcomes, supporting a key role for metabolic reprogramming. Mechanistically, ROS activates HIF-1\u03b1 and upregulates its downstream target LDHA, thereby linking metabolic reprogramming to placental dysfunction and highlighting this pathway as a potential therapeutic target. These findings reveal a mechanism underlying DENV-associated pregnancy complications and highlight metabolic pathways as potential therapeutic targets.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.00300-26","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T14:57:46Z","timestamp":1787324266000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Trophoblast metabolic reprogramming triggers adverse pregnancy outcomes during DENV-2 infection in mice"],"prefix":"10.1128","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5064-5616","authenticated-orcid":false,"given":"Han","family":"Wang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, School of Basic Medical Sciences, Capital 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