TY - JOUR
T1 - Epitope mapping and characterization of a novel CD4-induced human monoclonal antibody capable of neutralizing primary HIV-1 strains
AU - Xiang, Shi Hua
AU - Wang, Liping
AU - Abreu, Mariam
AU - Huang, Chih Chin
AU - Kwong, Peter D.
AU - Rosenberg, Eric
AU - Robinson, James E.
AU - Sodroski, Joseph
N1 - Funding Information:
We thank Yvette McLaughlin and Sheri Farnum for manuscript preparation. This work was supported by NIH Grants AI24755, AI31783, AI41851, and AI39420, by a Center for AIDS Research Grant AI28691, by an unrestricted research grant from the Bristol-Myers Squibb Foundation, by a gift from late William F. McCarty-Cooper, and by funds from the International AIDS Vaccine Initiative.
PY - 2003/10/10
Y1 - 2003/10/10
N2 - Human immunodeficiency virus (HIV-1) enters target cells by binding its gp120 exterior envelope glycoprotein to CD4 and one of the chemokine receptors, CCR5 or CXCR4. CD4-induced (CD4i) antibodies bind gp120 more efficiently after CD4 binding and block the interaction with the chemokine receptor. Examples of CD4i antibodies are limited, and the prototypes of the CD4i antibodies exhibit only weak neutralizing activity against primary, clinical HIV-1 isolates. Here we report the identification of a novel antibody, E51, that exhibits CD4-induced binding to gp120 and neutralizes primary HIV-1 more efficiently than the prototypic CD4i antibodies. The E51 antibody blocks the interaction of gp120-CD4 complexes with CCR5 and binds to a highly conserved, basic gp120 element composed of the β19-strand and surrounding structures. Thus, on primary HIV-1 isolates, this gp120 region, which has been previously implicated in chemokine receptor binding, is accessible to a subset of CD4i antibodies.
AB - Human immunodeficiency virus (HIV-1) enters target cells by binding its gp120 exterior envelope glycoprotein to CD4 and one of the chemokine receptors, CCR5 or CXCR4. CD4-induced (CD4i) antibodies bind gp120 more efficiently after CD4 binding and block the interaction with the chemokine receptor. Examples of CD4i antibodies are limited, and the prototypes of the CD4i antibodies exhibit only weak neutralizing activity against primary, clinical HIV-1 isolates. Here we report the identification of a novel antibody, E51, that exhibits CD4-induced binding to gp120 and neutralizes primary HIV-1 more efficiently than the prototypic CD4i antibodies. The E51 antibody blocks the interaction of gp120-CD4 complexes with CCR5 and binds to a highly conserved, basic gp120 element composed of the β19-strand and surrounding structures. Thus, on primary HIV-1 isolates, this gp120 region, which has been previously implicated in chemokine receptor binding, is accessible to a subset of CD4i antibodies.
KW - CD4-induced (CD4i) antibodies
KW - Envelope glycoprotein (gp120)
KW - Epitope mapping
KW - Human immunodeficiency virus (HIV-1)
KW - Human monoclonal antibody E51
KW - Neutralizing antibodies
KW - Primary HIV-1 isolates
KW - Soluble CD4 (sCD4)
KW - Structured treatment interruption (STI)
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U2 - 10.1016/S0042-6822(03)00521-X
DO - 10.1016/S0042-6822(03)00521-X
M3 - Article
C2 - 14592765
AN - SCOPUS:0242270786
SN - 0042-6822
VL - 315
SP - 124
EP - 134
JO - Virology
JF - Virology
IS - 1
ER -