Mack, Matthias and Pfirstinger, Jochen and Haas, Juergen and Nelson, Peter J. and Kufer, Peter and Riethmuller, Gert and Schlondorff, Detlef (2005) Preferential targeting of CD4-CCR5 complexes with bifunctional inhibitors: A novel approach to block HIV-1 infection. JOURNAL OF IMMUNOLOGY, 175 (11). pp. 7586-7593. ISSN 0022-1767,
Full text not available from this repository. (Request a copy)Abstract
Two receptors, CD4 and one of several chemokine receptors, are required for cellular HIV-1 infection, with CCR5 being the main coreceptor for macrophage-tropic strains. We have designed bifunctional fusion proteins, consisting of RANTES/CCL5 and a single-chain Fv Ab fragment against CD4 to simultaneously block CD4 and CCR5. The fusion proteins bind to both receptors, compete with RANTES/CCL5 binding, and induce down-modulation of CCR5 similar to 10 times more efficiently on CD4(+) compared with CD8(+) T cells. Moreover, after short incubation and subsequent washout, a significant down-modulation of CCR5 was only seen with the fusion proteins and only on CD4(+) cells, but not with unmodified RANTES or on CD4(-) cells, indicating a preferential targeting of CCR5 on CD4(+) T cells. The fusion proteins block M-tropic HIV infection more efficiently than RANTES/CCL5 and CD4 Abs alone or in combination. To our knowledge this is the first report of simultaneous blockade of an HIV-1 receptor and coreceptor with bifunctional inhibitors.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HUMAN-IMMUNODEFICIENCY-VIRUS; RECOMBINANT SOLUBLE CD4; CHEMOKINE RECEPTOR CCR5; MONOCLONAL-ANTIBODIES; TYPE-1 INFECTION; SMALL-MOLECULE; IN-VIVO; PHASE-I; RANTES; CELLS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Apr 2021 09:40 |
| Last Modified: | 14 Apr 2021 09:40 |
| URI: | https://pred.uni-regensburg.de/id/eprint/35373 |
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