{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T13:39:29Z","timestamp":1792676369023,"version":"4.5.0"},"reference-count":67,"publisher":"American Society for Microbiology","issue":"14","license":[{"start":{"date-parts":[[2009,7,15]],"date-time":"2009-07-15T00:00:00Z","timestamp":1247616000000},"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":[[2009,7,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The generation of humanized BLT mice by the cotransplantation of human fetal thymus and liver tissues and CD34\n                    <jats:sup>+<\/jats:sup>\n                    fetal liver cells into nonobese diabetic\/severe combined immunodeficiency mice allows for the long-term reconstitution of a functional human immune system, with human T cells, B cells, dendritic cells, and monocytes\/macrophages repopulating mouse tissues. Here, we show that humanized BLT mice sustained high-level disseminated human immunodeficiency virus (HIV) infection, resulting in CD4\n                    <jats:sup>+<\/jats:sup>\n                    T-cell depletion and generalized immune activation. Following infection, HIV-specific humoral responses were present in all mice by 3 months, and HIV-specific CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell responses were detected in the majority of mice tested after 9 weeks of infection. Despite robust HIV-specific responses, however, viral loads remained elevated in infected BLT mice, raising the possibility that these responses are dysfunctional. The increased T-cell expression of the negative costimulator PD-1 recently has been postulated to contribute to T-cell dysfunction in chronic HIV infection. As seen in human infection, both CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells demonstrated increased PD-1 expression in HIV-infected BLT mice, and PD-1 levels in these cells correlated positively with viral load and inversely with CD4\n                    <jats:sup>+<\/jats:sup>\n                    cell levels. The ability of humanized BLT mice to generate both cellular and humoral immune responses to HIV will allow the further investigation of human HIV-specific immune responses in vivo and suggests that these mice are able to provide a platform to assess candidate HIV vaccines and other immunotherapeutic strategies.\n                  <\/jats:p>","DOI":"10.1128\/jvi.02207-08","type":"journal-article","created":{"date-parts":[[2009,5,6]],"date-time":"2009-05-06T20:34:48Z","timestamp":1241642088000},"page":"7305-7321","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":264,"title":["Induction of Robust Cellular and Humoral Virus-Specific Adaptive Immune Responses in Human Immunodeficiency Virus-Infected Humanized BLT Mice"],"prefix":"10.1128","volume":"83","author":[{"given":"Diana M.","family":"Brainard","sequence":"first","affiliation":[{"name":"Center for Immunology and Inflammatory Diseases, Division of Rheumatology, 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