Autocrine interferon-β synthesis for gene therapy of HIV infection

Vieillard, Vincent; Lauret, Evelyne; Maguer, Véronique; Jacomet, Christine; Rozenbaum, Willy; Gazzolo, Louis; Maeyer, Edward De

doi:10.1097/00002030-199511000-00002

Cited by 17 publications

(8 citation statements)

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“…Allogeneic CD4 1 T cells were isolated from peripheral blood mononuclear cells (PBMCs) from healthy donors as previously described (Vieillard et al, 1995).…”

Section: Collection and Purification Of Cord Blood Cd34 1 Cells And Omentioning

confidence: 99%

“…HIVLAI stock was prepared as previously described (Vieillard et al, 1995). Untransduced or IFN-b -transduced DCs (10 5 cells) were cultured in 200 m l of medium, in 96-well roundbottom microtiter plates, and were pulsed with HIVLAI for 3 hr at 37°C, at a multiplicity of infection (MOI) of approximately 0.01, and then washed three times.…”

Section: Hiv Resistance Analysismentioning

confidence: 99%

“…Untransduced or IFN-b -transduced DCs (10 5 cells) were cultured in 200 m l of medium, in 96-well roundbottom microtiter plates, and were pulsed with HIVLAI for 3 hr at 37°C, at a multiplicity of infection (MOI) of approximately 0.01, and then washed three times. When mixtures of DCs and CD4 1 T cells were studied, HIV-pulsed DCs (3 3 10 4 cells) were mixed with 6 3 10 4 allogeneic CD4 1 T cells, non-HIV pulsed, which had been previously activated with phytohem agglutinin (PHA) and IL-2 as previously described (Vieillard et al, 1995), in 200 m l in 96-well round-bottom microtiter plates. Uninfected cell populations were run in parallel.…”

Section: Hiv Resistance Analysismentioning

confidence: 99%

“…Serial 10-fold dilutions of DNA preparations from HIVLAI-infected J. Jhan cells containing one copy of HIV per cell and from plasmid-transfected U937 cells containing one copy of IFN-b transgene per cell (Mace et al, 1991;Vieillard et al, 1995), were used as standards and amplified in each reaction to determine interassay variability and sensitivity. The reaction products were detected by autoradiography after electrophoresis on 4% polyacrylamide gels.…”

Section: Pcr Analysis For Detection Of Ifn-b Transgene and Hiv Dna Comentioning

confidence: 99%

“…The advantage of constitutive expression, as opposed to the natural production of IFN, which only takes place after viral infection has occurred, is the establishment of a perm anent antiviral state in the transduced cells. It has previously been shown that this procedure strongly inhibits HIV replication and progression of infection in lymphocyte suspensions derived from HIV-infected donors, that it enhances the production of Th1-type cytokines, and that it improves the proliferative response to recall antigens (Vieillard et al, 1995(Vieillard et al, , 1997. Moreover, IFNb transduction of CD8 1 T cells enhances their HIV-1-specific cytolytic effects through an upregulation of RANTES production (Hadida et al, 1999).…”

Section: Introduction C U R R En T H Ig H Ly a C Tiv E Antiretroviralmentioning

confidence: 99%

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

Cremer

Vieillard²,

Sautès-Fridman

et al. 2000

Human Gene Therapy

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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.

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“…Allogeneic CD4 1 T cells were isolated from peripheral blood mononuclear cells (PBMCs) from healthy donors as previously described (Vieillard et al, 1995).…”

Section: Collection and Purification Of Cord Blood Cd34 1 Cells And Omentioning

confidence: 99%

Section: Hiv Resistance Analysismentioning

confidence: 99%

Section: Hiv Resistance Analysismentioning

confidence: 99%

Section: Pcr Analysis For Detection Of Ifn-b Transgene and Hiv Dna Comentioning

confidence: 99%

Section: Introduction C U R R En T H Ig H Ly a C Tiv E Antiretroviralmentioning

confidence: 99%

See 3 more Smart Citations

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

Cremer

Vieillard²,

Sautès-Fridman

et al. 2000

Human Gene Therapy

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Type I Interferon Is a Powerful Inhibitor of in Vivo HIV-1 Infection and Preserves Human CD4+ T Cells from Virus-Induced Depletion in SCID Mice Transplanted with Human Cells

et al. 1999

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Although several studies are available on the in vitro inhibitory activities of type I interferon (IFN) on HIV-1 replication, the role of these cytokines in the pathogenesis of AIDS is still matter of conjecture. Both beneficial and adverse effects have been envisaged and considered as a possible rationale for the development of either IFN or anti-IFN therapies in HIV-1-infected patients. In the present study, we have evaluated the efficacy of human type I IFN on HIV-1 infection and virus-induced depletion of human CD4 T cells in two models established in SCID mice. In SCID mice transplanted with human U937 cells (U937-SCID mouse model), continuous treatment with type I consensus IFN (CIFN) resulted in a total suppression of HIV-1 infection. This inhibitory effect was superior to that obtained after AZT treatments. Results from an ensemble of experiments in SCID mice transplanted with either control or genetically modified human U937 cells transduced with a Tat-inducible IFN-alpha gene (LTR-IFN-A2 U937) indicated that low levels of IFN-alpha, produced locally as a result of virus infection, were extremely effective in inhibiting acute HIV infection and virus replication. Of interest, LTR-IFN-A2 U937 cells conferred a strong anti-HIV-1 protection to coinjected bystander U937 cells. Notably, experiments with SCID mice reconstituted with human PBL (hu-PBL-SCID mouse model) showed that treatment with CIFN inhibited HIV-1 replication more effectively than AZT treatment. Remarkably, treatment with CIFN resulted in a clear-cut protection from the virus-induced depletion of human CD4 T cells, which was also associated with the generation of an antibody response toward HIV-1 antigens in 50% of the virus-injected xenografts. These results suggest that type I IFN efficiently preserves human CD4(+) cells from virus-induced damage in hu-PBL-SCID mice, not only by inducing an antiviral state in target cells but also by stimulating anti-HIV-1 human immune responses in vivo.

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T-Bodies as Antiviral Agents

Bitton¹,

Debré²,

Eshhar³

et al. 2001

Current Topics in Microbiology and Immunology

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Autocrine interferon-β synthesis for gene therapy of HIV infection

Cited by 17 publications

References 0 publications

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

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

Type I Interferon Is a Powerful Inhibitor of in Vivo HIV-1 Infection and Preserves Human CD4+ T Cells from Virus-Induced Depletion in SCID Mice Transplanted with Human Cells

T-Bodies as Antiviral Agents

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Autocrine interferon-β synthesis for gene therapy of HIV infection

Cited by 17 publications

References 0 publications

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

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

Type I Interferon Is a Powerful Inhibitor of in Vivo HIV-1 Infection and Preserves Human CD4+ T Cells from Virus-Induced Depletion in SCID Mice Transplanted with Human Cells

T-Bodies as Antiviral Agents

Contact Info

Product

Resources

About

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

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