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
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
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
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
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
Amic changes in conformation and function of the HIV-1 envelope glycoproteins, immediately after engagement of the activating molecules. Using these tools, we found that SCMs inactivate envelope glycoprotein function by an activation-triggered inhibition process, through induction of a metastable activated state.Materials and Methods Reagents and AntibodiesFour-domain sCD4 (molecular weight 50 kDa
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
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