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
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
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
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
To current convention [46]). C34-Ig was produced and purified as previously described [47]. The CD4-Ig fusion protein consists of the first two N-terminal domains of the CD4 molecule and the Fc region of human IgG1. Purification was carried out as described for the C34-Ig molecule [47].mechanism of sCD4 neutralization [17,18]. Resistance to sCD4 may thus arise by a decreased affinity of the envelo
To current convention [46]). C34-Ig was produced and purified as previously described [47]. The CD4-Ig fusion protein consists of the first two N-terminal domains of the CD4 molecule and the Fc region of human IgG1. Purification was carried out as described for the C34-Ig molecule [47].mechanism of sCD4 neutralization [17,18]. Resistance to sCD4 may thus arise by a decreased affinity of the envelo
E sCD4 concentrations that are required to elicit shedding are significantly higher than those required to neutralize the virus [25,26]. In addition, for some HIV-1 strains, the temperature dependence of sCD4-induced gp120 shedding and virus neutralization differs [26]. The mode of sCD4-mediated inhibition thus remains incompletely understood. Targeting the functionally important and therefore con
E sCD4 concentrations that are required to elicit shedding are significantly higher than those required to neutralize the virus [25,26]. In addition, for some HIV-1 strains, the temperature dependence of sCD4-induced gp120 shedding and virus neutralization differs [26]. The mode of sCD4-mediated inhibition thus remains incompletely understood. Targeting the functionally important and therefore con