Inhibition of human immunodeficiency virus transmission to CD4+ T cells after gene transfer of constitutively expressed interferon beta to dendritic cells.
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-beta 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-beta production by DCs increases the synthesis of IL-12 and IFN-gamma Th1-type cytokines and of the beta-chemokines MIP-1alpha, MIP-1beta, and RANTES. This indicates that IFN-beta transduction of DCs blocks HIV infection and viral transmission to CD4(+) T cells, and could favor cellular immune responses in HIV-infected patients.
Cremer
I
I
Laboratorie d'Immunologie Cellulaire et Clinique, INSERM U255, Institut Curie, Paris, France. Isabelle.Cremer@curie.fr
Vieillard
V
V
Sautès-Fridman
C
C
De Maeyer
E
E
D018952:Antigens, CD34 / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000096:biosynthesis; D003588:Cytopathogenic Effect, Viral; D003713:Dendritic Cells / Q000378:metabolism / Q000821:virology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D018014:Gene Transfer Techniques; D006678:HIV / Q000472:pathogenicity*; D015658:HIV Infections / Q000635:transmission*; D006801:Humans; D016899:Interferon-beta / Q000235:genetics* / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis; D016133:Polymerase Chain Reaction
D018952:Antigens, CD34; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D007376:Interleukin-2; D019402:Macrophage Inflammatory Proteins; D016899:Interferon-beta; D007371:Interferon-gamma