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
GCl2, 25 mM Tris, pH 7.5 and 140 mM NaCl). For pulse activation experiments, the COS-1 cells were incubated with sCD4 (40 mg/ml, 0.8 mM) or 191 (360 mM) suspended in blocking buffer for three minutes, washed three times with blocking buffer and incubated for different time periods until the C34-Ig or 48d antibodies were added (at 40 mg/ml or 1 mg/ml, respectively, for 30 minutes). To study the tem
D role functioning (perfect score = 100) favoured the CXT arm (median change HAART = 0, CXT = +17; p=0.011). Improvement in pain (perfect score = 0, median change HAART = -16.7, CXT = -33.3; p=0.1) and overall QOL (median change HAART = 12.5, CXT = 16.7; p=0.08) were also greater in the CXT arm. Comparisons between arms were not statistically significant.NIH-PA Author Manuscript NIH-PA Author Manu
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
Ion, was used as a negative control. The YU2(Dct) protein has a truncated cytoplasmic tail of 17 amino acids, with a stop codon introduced after Ala 710 (numbered according to current convention [46]). The YU2-GS8 construct is a cleavage-defective form of the YU2 HIV-1 envelope glycoproteins that contains an 8-amino acid glycine-serine linker at the gp120/gp41 junction. Starting with the cytoplasm
Ion, was used as a negative control. The YU2(Dct) protein has a truncated cytoplasmic tail of 17 amino acids, with a stop codon introduced after Ala 710 (numbered according to current convention [46]). The YU2-GS8 construct is a cleavage-defective form of the YU2 HIV-1 envelope glycoproteins that contains an 8-amino acid glycine-serine linker at the gp120/gp41 junction. Starting with the cytoplasm
Ibited highly stable sCD4-induced intermediates that did not appreciably decay at room temperature for up to 1 hour after the sCD4 pulse. For these envelope glycoproteins, the half-lives of the HR1-exposed state measured at 37uC were 16 and 17 minutes, respectively (Figure S2D).Correlation between Stability of the HR1 Groove and Functional Stability of the HIV-1 Envelope Glycoproteins after sCD4 E
D role functioning (perfect score = 100) favoured the CXT arm (median change HAART = 0, CXT = +17; p=0.011). Improvement in pain (perfect score = 0, median change HAART = -16.7, CXT = -33.3; p=0.1) and overall QOL (median change HAART = 12.5, CXT = 16.7; p=0.08) were also greater in the CXT arm. Comparisons between arms were not statistically significant.NIH-PA Author Manuscript NIH-PA Author Manu