Interferon-γ Is Associated with the Surface of the Human Immunodeficiency Virus and Binds to the<i>gag</i>Gene Product p17

Caruso, Arnaldo; Pollara, P.; Foresti, I; Bonfanti, Carlo; Francesco, Maria Antonia De; Gelmi, M; Turano, A

doi:10.1089/aid.1989.5.605

Cited by 12 publications

(3 citation statements)

References 23 publications

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“…However, previous in vitro studies have reported conflicting results: some authors observed an inhibition of HIV replication and cytopathogenicity by IFN-y [12,131,while others foundno effect [14]. These discrepancies may be due to the simultaneous production of HIV and IFN-y by some infected cells [15], a situation which does not allow a total control of experimental conditions. From a fundamental point of view, the HT29 cell line represents a good model for studying the effect of IFN-y on HIV infection because it responds to the following criteria: (a) these cells, of epithelial origin, do not synthesize IFN-y; (b) they express functional receptors for IFN-y [16] and (c) they can be productively infected by HIV-1 and HIV-2 strains [lo].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of human immunodeficiency virus infection in human colon epithelial cells by recombinant interferon‐γ

et al. 1992

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Pretreatment of human colon epithelial cells HT29 by recombinant gamma interferon (IFN)-gamma was found to protect the cells from infection with various isolates of human immunodeficiency virus (HIV)-1 and HIV-2, as assessed by co-cultivation with human T lymphoblastoid cells and gene amplification by polymerase chain reaction technique. Additionally, IFN-gamma induced a dose-dependent inhibition of HIV-1 and HIV-2 production in chronically infected HT29 cells. In situ hybridization studies demonstrated that IFN-treated cells were still able to synthesize viral messenger ribonucleic acid. However, the expression of the p24 product of the gag gene was markedly decreased after IFN treatment as demonstrated by radio-immunoprecipitation assay. Taken together, these data suggested that the cytokine acted at the post-translational level by inhibiting the processing of structural viral proteins. It is concluded from this study that IFN-gamma has a potent anti-HIV effect on epithelial gastrointestinal cells.

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Section: Introductionmentioning

confidence: 99%

Inhibition of human immunodeficiency virus infection in human colon epithelial cells by recombinant interferon‐γ

et al. 1992

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“…We previously demonstrated that the HIV-1 matrix protein p17 was able to interact with human IFN-␥ without affecting its biological properties (17,18). Apparently this interaction is caused by structural similarities between p17 and IFN-␥ (19).…”

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confidence: 99%

HIV-1 matrix protein p17 increases the production of proinflammatory cytokines and counteracts IL-4 activity by binding to a cellular receptor

Francesco

Baronio

Fiorentini

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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Purified recombinant HIV-1 p17 matrix protein significantly increased HIV-1 replication in preactivated peripheral blood mononuclear cell cultures obtained from healthy donors. Because HIV-1 infection and replication is related to cell activation and differentiation status, in the present study, we investigated the role played by p17 during the process of T cell stimulation. Using freshly isolated peripheral blood mononuclear cells, we demonstrate that p17 was able to enhance levels of tumor necrosis factor ␣ and IFN-␥ released from cells stimulated by IL-2. IL-4 was found to downregulate IFN-␥ and tumor necrosis factor ␣, and p17 restored the ability of cells to produce both cytokines. The property of p17 to increase production of proinflammatory cytokines could be a mechanism exploited by the virus to create a more suitable environment for HIV-1 infection and replication. Our data show that p17 exerts its biological activity after binding to a specific cellular receptor expressed on activated T lymphocytes. The functional p17 epitope involved in receptor binding was found to be located at the NH 2-terminal region of viral protein. Immunization of BALB͞c mice with a 14-aa synthetic peptide representative of the HIV-1 p17 functional region (SGGELDRWEKIRLR) resulted in the development of p17 neutralizing antibodies capable of blocking the interaction between p17 and its cellular receptor. Our results define a role for p17 in HIV-1 pathogenesis and contribute to our understanding of the molecular mechanism of HIV-1 infection and the development of additional antiviral therapeutic strategies.

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“…HIV-1 matrix protein p17 shows structural similarities with the proinflammatory cytokine interferon (IFN)-␥, 11 but it does not bind to the IFN-␥ cellular receptor. 12 More recently, we have shown that p17 can be considered a viral cytokine since it is capable of increasing proliferation of interleukin (IL)-2-or phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) and enhance HIV-1 replication.…”

Section: Introductionmentioning

confidence: 99%

Preclinical studies on immunogenicity of the HIV‐1 p17‐based synthetic peptide AT20‐KLH

et al. 2004

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Several studies have suggested that HIV-1 p17 matrix protein may play an important role in AIDS pathogenesis, since anti-p17 antibodies represent a serological marker of disease progression during HIV-1 infection both in adults and children. Moreover, it has been recently reported that the viral protein is capable of significantly increasing the proliferation of preactivated T lymphocytes and the release of proinflammatory cytokines. Recombinant HIV-1 p17 also has induced an increased rate of HIV-1 replication in vitro. All p17 biological activities are exerted after its binding to a specific cellular receptor expressed on activated T lymphocytes. The functional p17 epitope involved in receptor binding was found to be located at the NH(2)-terminal region of the viral protein. Immunization of C57BL/6 mice with a 20 amino acid synthetic peptide representative of the HIV-1 p17 functional region (AT20) coupled to the carrier protein keyhole limpet hemocyanin (KLH) and given in Freund's incomplete adjuvant, resulted in the development of p17-neutralizing antibodies capable of blocking p17/p17 receptor interaction, and consequently, all biological activities of the viral protein. Moreover, it was possible to skew the humoral response induced by priming mice with AT20-KLH toward cell-mediated immune responses, boosting animals with p17. Our findings may provide a new strategy to develop a synthetic AIDS vaccine based on a potentially effective and safe subunit vaccine against the HIV-1 cytokine-like matrix protein p17. Preclinical immunogenicity data for AT20-KLH provide the basis for evaluation of the peptide-based vaccine, alone and in combination with p17 or p17 DNA vaccines, in Phase I clinical trials.

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Interferon-γ Is Associated with the Surface of the Human Immunodeficiency Virus and Binds to thegagGene Product p17

Cited by 12 publications

References 23 publications

Inhibition of human immunodeficiency virus infection in human colon epithelial cells by recombinant interferon‐γ

Inhibition of human immunodeficiency virus infection in human colon epithelial cells by recombinant interferon‐γ

HIV-1 matrix protein p17 increases the production of proinflammatory cytokines and counteracts IL-4 activity by binding to a cellular receptor

Preclinical studies on immunogenicity of the HIV‐1 p17‐based synthetic peptide AT20‐KLH

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