Transfer of Human CD4+ T Lymphocytes Producing Beta Interferon in Hu-PBL-SCID Mice Controls Human Immunodeficiency Virus Infection

AUTOR(ES)

Vieillard, Vincent

FONTE

American Society for Microbiology

RESUMO

Beta interferon (IFN-β) exerts pleiotropic antiretroviral activities and affects many different stages of the human immunodeficiency virus (HIV) infectious cycle in IFN-treated cells. To explore whether transfer of genetically engineered human CD4+ T cells producing constitutively low amounts of IFN-β can eradicate HIV in vivo, we developed a new Hu-PBL-SCID mouse model supporting a persistent, replicative HIV infection maintained by periodic reinoculations of activated human CD4+ T cells. Transferring human CD4+ T cells containing the IFN-β retroviral vector drastically reduced the preexisting HIV infection and enhanced CD4+ T-cell survival and Th1 cytokine expression. Furthermore, in 40% of the Hu-PBL-SCID mice engrafted with IFN-β-transduced CD4+ T cells, HIV-1 was undetectable in vivo as well as after cocultivation of mouse tissues with human phytohemagglutinin-stimulated lymphoblasts. These results indicate that a therapeutic strategy based upon IFN-β transduction of CD4+ T cells may be an approach to controlling a preexisting HIV infection and allowing immune restoration.

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