HIV replication can be blocked by recombinant human interferon beta

Michaelis, Barbara; Levy, Jay A.

doi:10.1097/00002030-198903010-00006

Cited by 45 publications

(11 citation statements)

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“…Efforts have been made to identify and characterize the anti-HIV tymphokine produced by CD8ĉ ells. None of a panel of known lymphokines tested inhibited HIV replication in vitro in a manner consistent with that of the CD8^ cell-produced factor [29][30][31][32]. These findings suggest that this activity is mediated by a novel cytokine.…”

Section: Introductionmentioning

confidence: 84%

Inhibition of HIV replication by CD8+ T cells correlates with CD4 counts and clinical stage of disease

Gómez

Smaill

Rosenthal

1994

Clinical and Experimental Immunology

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SUMMARY We sought to evaluate the relationship of CD8+ T cell‐mediated inhibition of autologous HIV replication in vitro to disease stage in HIV+ individuals. Depletion of CD8+ T cells from peripheral blood lymphocytes of 16 HIV+ subjects increased the percentage of virus‐producing cultures from 56% to 81%. CD4+ T cells were purified from 52 HIV+ individuals and cultured alone or in the presence of autologous CD8+ T cells. In 13 (25%) subjects HIV replication was only detected in the absence of CD8+ T cells (inhibition positive); in 26 (50%) viral replication occurred both in the absence and presence of CD8+ cells (inhibition negative). In the remaining 13 (25%) subjects, CD8+ T cell‐mediated inhibitory activity could not be evaluated because stimulation of their purified CD4+ T cells did not result in p24 production. In some virus culture‐negative individuals, the inability to demonstrate HIV replication was due to the presence of low numbers of CD8+ T cells that co‐purified with CD4+ T cells. Detection of inhibitory CD8+ T cells was associated with significantly higher CD4 counts and better clinical status compared with inhibition‐negative subjects. These results demonstrate that CD8+ T cell‐mediated inhibition of HIV replication correlates with disease stage, and thus may play a role in preventing disease progression. CD8+ T cells did not inhibit autologous HIV replication across a semipermeable membrane. Further, the ability of CD8+ T cells to prevent HIV replication did not correlate with lysis of autologous CD4+ T cells. Thus, CD8+ T cells inhibited autologous HIV replication in vitro through a contact mediated non‐lytic mechanism.

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Section: Introductionmentioning

confidence: 84%

Inhibition of HIV replication by CD8+ T cells correlates with CD4 counts and clinical stage of disease

Gómez

Smaill

Rosenthal

1994

Clinical and Experimental Immunology

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“…However, during the treatment, a low replication of HIV goes on in lymphoid organs. In the present work, our design consisted of producing an anti-HIV resistant state in macrophages as a therapeutic approach to HIV disease through a low continuous production of IFN-␤ that affects several stages of the HIV life cycle in infected macrophages (7)(8)(9)(10) and results in inhibition of HIV replication. For this purpose, macrophages were transduced by a retroviral vector (HMB-K b HuIFN␤) carrying the human IFN-␤ coding sequence driven by a fragment of the H-2K b MHC gene promoter (11).…”

Section: Retrovirally Mediated Ifn-␤ Transduction Of Macrophagesmentioning

confidence: 99%

Retrovirally Mediated IFN-β Transduction of Macrophages Induces Resistance to HIV, Correlated with Up-Regulation of RANTES Production and Down-Regulation of C-C Chemokine Receptor-5 Expression

Cremer

Vieillard

Maeyer

2000

The Journal of Immunology

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Constitutive expression of IFN-β by HIV target cells may be an alternative or complementary therapeutic approach for the treatment of AIDS. We show that macrophages derived from CD34+ cells from umbilical cord blood can be efficiently transduced by a retroviral vector carrying the IFN-β coding sequence. This results in resistance to infection by a macrophage-tropic HIV type 1, as shown by the drastic reduction in the HIV DNA copy number per cell and in p24 release. Moreover, IFN-β transduction totally blocked secretion of proinflammatory cytokines after HIV infection. The constitutive IFN-β production also resulted in an increased production of IL-12 and IFN-γ Th1-type cytokines and of the β-chemokines macrophage-inflammatory protein-1α, macrophage-inflammatory protein-1β, and RANTES. RANTES was found to be involved in the HIV resistance observed, and this was correlated with a down-regulation of the CCR-5 HIV entry coreceptor. These results demonstrate the feasibility and the efficacy of such IFN-β-mediated gene therapy. In addition to inhibiting HIV replication, IFN-β transduction could have beneficial immune effects in HIV-infected patients by favoring cellular immune responses.

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“…Other directions for antiviral therapy include attacks on the viral cellular receptor by using recombinant CD4, blocking virus attachment with sulfated polysaccharides (43,751), the use of interferons (469,783,935), and approaches that destroy the virusinfected cells (73,643) (Table 35 (263,767,768,999). Nevertheless, resistance to these drugs could also emerge (878).…”

Section: Features Of Hiv Pathogenesismentioning

confidence: 99%