{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T23:05:21Z","timestamp":1773270321236,"version":"3.50.1"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2008,1,1]],"date-time":"2008-01-01T00:00:00Z","timestamp":1199145600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Macrophages serve as a major reservoir for HIV-1 because a large number of macrophages in the brain and lung are infected with HIV-1 during late stage disease. Recent evidence suggests that those HIV-1-infected macrophages play a key role in contributing to tissue damage in AIDS pathogenesis. Macrophages undergo apoptosis upon HIV-1 infection; however, the mechanisms of this process are not well-defined. Previously, we demonstrated that HIV-1 infection inhibits Akt-1, a critical protein for cell survival of macrophages. In the present study, we investigated the involvement of transcription factor FOXO3a in the regulation of HIV-1-mediated apoptosis in macrophages. HIV-1 infection significantly decreased phosphorylation of FOXO3a and promoted FOXO3a translocation to the nucleus in human monocyte-derived macrophages (MDM). Overexpression of a constitutively active FOXO3a increased DNA fragmentation with decreased cell viability in MDM, whereas a dominant-negative mutant of FOXO3a or small interfering RNA for FOXO3a to knockdown the function of FOXO3a in HIV-1-infected MDM decreased DNA fragmentation and protected macrophages from death in HIV-1-infected MDM. Overexpression of constitutively active Akt-1 increased FOXO3a phosphorylation, suggesting that FOXO3a phosphorylation in human MDM is dependent on Akt-1. We therefore conclude that FOXO3a plays an important role in HIV-1-induced cell death of human macrophage. Understanding the PI3K\/Akt-1\/FOXO3a pathway and its associated death mechanism in macrophages during HIV-1 infection would lead to identification of potential therapeutic avenues for the treatment of HIV-1 infection.<\/jats:p>","DOI":"10.4049\/jimmunol.180.2.898","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T23:09:13Z","timestamp":1397862553000},"page":"898-906","source":"Crossref","is-referenced-by-count":40,"title":["Transcription Factor FOXO3a Mediates Apoptosis in HIV-1-Infected Macrophages"],"prefix":"10.1093","volume":"180","author":[{"given":"Min","family":"Cui","sequence":"first","affiliation":[{"name":"Laboratory of Neurotoxicology, University of Nebraska Medical Center , Omaha, NE 68198"},{"name":"Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center , Omaha, NE 68198"},{"name":"Transplantation Biology Research Division, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences , Beijing ,","place":["China"]},{"name":"The China-U.S. Joint Research Center for Life Sciences , Beijing ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunlong","family":"Huang","sequence":"additional","affiliation":[{"name":"Laboratory of Neurotoxicology, University of Nebraska Medical Center , Omaha, NE 68198"},{"name":"Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center , Omaha, NE 68198"},{"name":"The China-U.S. Joint Research Center for Life Sciences , Beijing ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Laboratory of Neurotoxicology, University of Nebraska Medical Center , Omaha, NE 68198"},{"name":"Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center , Omaha, NE 68198"},{"name":"Transplantation Biology Research Division, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences , Beijing ,","place":["China"]},{"name":"The China-U.S. Joint Research Center for Life Sciences , Beijing ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jialin","family":"Zheng","sequence":"additional","affiliation":[{"name":"Laboratory of Neurotoxicology, University of Nebraska Medical Center , Omaha, NE 68198"},{"name":"Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center , Omaha, NE 68198"},{"name":"Department of Pathology and Microbiology, University of Nebraska Medical Center , Omaha, NE 68198"},{"name":"Transplantation Biology Research Division, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences , Beijing ,","place":["China"]},{"name":"The China-U.S. Joint Research Center for Life Sciences , Beijing ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2008,1,15]]},"reference":[{"key":"2025032610020909000_R1","first-page":"1354","volume-title":"J. 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