Decker J.M., Bibollet Ruche F., Wei X.P., Wang S.Y., Levy D.N., Wang W.Q., Delaporte Eric, Peeters Martine, Derdeyn C.A., Allen S., Hunter E., Saag M.S., Hoxie J.A., Hahn B.H., Kwong P.D., Robinson J.E., Shaw G.M. (2005). Antigenic conservation and immunogenicity of the HIV coreceptor binding site. Journal of Experimental Medicine, 201 (9), p. 1407-1419. ISSN 0022-1007.
Titre du document
Antigenic conservation and immunogenicity of the HIV coreceptor binding site
Année de publication
2005
Auteurs
Decker J.M., Bibollet Ruche F., Wei X.P., Wang S.Y., Levy D.N., Wang W.Q., Delaporte Eric, Peeters Martine, Derdeyn C.A., Allen S., Hunter E., Saag M.S., Hoxie J.A., Hahn B.H., Kwong P.D., Robinson J.E., Shaw G.M.
Source
Journal of Experimental Medicine, 2005,
201 (9), p. 1407-1419 ISSN 0022-1007
Immunogenic, broadly reactive epitopes of the HIV-1 envelope glycoprotein could serve as important targets of the adaptive humoral immune response in natural infection and, potentially, as components of an acquired immune deficiency syndrome vaccine. However, variability in exposed epitopes and a combination of highly effective envelope-cloaking strategies have made the identification of such epitopes problematic. Here, we show that the chemokine coreceptor binding site of HIV-1 from clade A, B, C, D, F, G, and H and circulating recombinant form (CRF)01, CRF02, and CRF11, elicits high titers of CD4-induced (CD4i) antibody during natural human infection and that these antibodies bind and neutralize viruses as divergent as HIV-2 in the presence of soluble CD4 (sCD4). 178 out of 189 (94%) HIV-1-infected patients had CD4i antibodies that neutralized sCD4-pretreated HIV-2 in titers (50% inhibitory concentration) as high as 1:143,000. CD4i monoclonal antibodies elicited by HIV-1 infection also neutralized HIV-2 pretreated with sCD4, and polyclonal antibodies from HIV-1-infected humans competed specifically with such monoclonal antibodies for binding. In vivo, variants of HIV-1 with spontaneously exposed coreceptor binding surfaces were detected in human plasma; these viruses were neutralized directly by CD4i antibodies. Despite remarkable evolutionary diversity among primate lentiviruses, functional constraints on receptor binding create opportunities for broad humoral immune recognition, which in turn serves to constrain the viral quasispecies.
Plan de classement
Entomologie médicale / Parasitologie / Virologie [052]
Localisation
Fonds IRD [F B010042956]
Identifiant IRD
fdi:010042956
