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
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
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
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
Tagonist `Compound A' [4-nitrobenzyl 1-(3(N-methylphenylsulfonamido)-3-phenylbutyl)piperidin-4-yl(vinyl)carbamate] [41,42] was kindly provided by Dr. Martin Springer at Merck Research Laboratories, Rahway, NJ. The anti-gp120 monoclonal antibody 48d, which recognizes an epitope that overlaps the coreceptor-binding site, was kindly provided by Dr. James Robinson (Tulane University Medical Center) [4
Effects of inflammation on health during chronic HIV infection. Immunity 2013; 39: 633?45. 55. Kuller LH, Tracy R, Belloso W, De Wit S, Drummond F, Lane HC et al. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med 2008; 5: e203. 56. Neuhaus J, Jacobs Jr DR, Baker JV, Calmy A, Duprez D, La Rosa A et al. Markers of inflammation, coagulation, and renal func
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