Inhibition of Human Immunodeficiency Virus Transmission to CD4 + T Cells after Gene Transfer of Constitutively Expressed Interferon β to Dendritic Cells

Abstract

CD34⁺-derived dendritic cells (DCs) can be infected by the T cell-tropic HIVLAI strain, but are poorly permissive for efficient virus production. However, HIVLAI-infected DCs are able to transmit a vigorous cytopathic infection to activated CD4⁺ T cells. We show that DCs differentiated from CD34⁺ cells can be efficiently transduced by a retroviral vector carrying the IFN-β coding sequence. This results in resistance to infection by HIV as shown by a threefold reduction in the HIV DNA copy number per cell, and by inhibition of HIV transmission from DCs to CD4⁺ T cells. Moreover, constitutive IFN-β production by DCs increases the synthesis of IL-12 and IFN-γ Th1-type cytokines and of the β-chemokines MIP-1α, MIP-1β, and RANTES. This indicates that IFN-β transduction of DCs blocks HIV infection and viral transmission to CD4⁺ T cells, and could favor cellular immune responses in HIV-infected patients.