Infection in vitro, this protein was tested for clinical efficacy in HIV-1-infected individuals; however, no effect on plasma viral loads was observed [13]. Further examination revealed that doses of sCD4 that were significantly higher than those achieved in the clinical trial were required to neutralize primary clinical isolates of HIV-1, in contrast to the relatively sensitive, laboratory-adapte
Coproteins [1]. Binding of gp120 to the receptor, CD4, on the target cell surface induces major conformational changes in the envelope glycoproteins [2]. These changes allow gp120 to bind the viral coreceptor, either CXCR4 or CCR5 [3?]. CD4 binding also induces the formation of a gp41 pre-hairpin intermediate, in which three hydrophobic grooves on the surface of a coiled coil formed by the heptad
Coproteins [1]. Binding of gp120 to the receptor, CD4, on the target cell surface induces major conformational changes in the envelope glycoproteins [2]. These changes allow gp120 to bind the viral coreceptor, either CXCR4 or CCR5 [3?]. CD4 binding also induces the formation of a gp41 pre-hairpin intermediate, in which three hydrophobic grooves on the surface of a coiled coil formed by the heptad
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Ied [31,32]. These compounds, which include the prototypic compound NBD556 and its derivatives, mimic the effects of CD4 by inducing the exposure of the coreceptor-binding site on gp120 [31,33]. Although NBD-556 inhibits HIV-1 infection of CD4+CCR5+ cells, it can replace CD4 and thus enhance HIV-1 infection of CD42CCR5+ cells [31]. In view of their capacity to enhance infectivity, any potential ap
Port, we show that soluble mimics of CD4 inhibit HIV-1 infection by prematurely triggering the viral envelope glycoproteins. The unstable activated state of the virus lasts only a few minutes, after which the virus loses the ability to infect cells. This novel strategy for inhibition may be generally applicable to other viruses besides HIV-1, some of which are also activated by binding to their re
Coproteins [1]. Binding of gp120 to the receptor, CD4, on the target cell surface induces major conformational changes in the envelope glycoproteins [2]. These changes allow gp120 to bind the viral coreceptor, either CXCR4 or CCR5 [3?]. CD4 binding also induces the formation of a gp41 pre-hairpin intermediate, in which three hydrophobic grooves on the surface of a coiled coil formed by the heptad
ErcialNoDerivs 3.0 Unported License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://cr