[Role of chemokines in the HIV infection process].
In order to infect a target cell, the HIV envelope glycoprotein gp 120 has to interact with both the cellular receptor CD4 and an HIV-coreceptor, i.e. the CC or CXC chemokine receptor CCR5 or CXCR4. Both coreceptors were immediately recognized as novel targets for anti-HIV-therapy. Blocking these coreceptors would protect the cell from viral entry and would reduce the viral transmission and pathogenesis. Here we describe the purification and characterization of natural chemokine variants and compare their antiviral activity. In addition, the role of proteases for the processing of the CC chemokines RANTES, eotaxin, MDC and MIP-1 alpha and of the CXC chemokine SDF-1 are studied. The MIP-1 alpha-isoform LD78 beta, that was purified form natural sources, inhibited HIV-infection completely in CCR5-transfected cells, mononuclear leukocytes and purified monocytes at low (ng/ml) concentrations. This research will make it feasible to develop specific chemokine-analogs that block HIV-entry. Deciphering the processes that play a role during the complicated interactions between HIV-gp120 and the cellular membrane may lead to a more efficient treatment of HIV-infections.
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Rega Instituut, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
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D018925:Chemokines / Q000502:physiology*; D006678:HIV / Q000276:immunology* / Q000502:physiology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D006801:Humans; D019713:Receptors, CCR5 / Q000378:metabolism / Q000502:physiology; D019718:Receptors, CXCR4 / Q000378:metabolism / Q000502:physiology; D015728:Receptors, HIV / Q000502:physiology*; D014779:Virus Replication
D018925:Chemokines; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D015728:Receptors, HIV