Antibody-mediated enhancement of human immunodeficiency virus type 1 infectivity is determined by the structure of gp120 and depends on modulation of the gp120-CCR5 interaction
In this study, we characterized the viral determinants of coreceptor usage in relation to susceptibility to antibody-mediated neutralization or enhancement of infectivity by using chimeras of three highly related human immunodeficiency virus type 1 (HIV-1) isolates of different phenotypes. We found that the V3 region was the main determinant of antibody-mediated enhancement and coreceptor specificity but that the overall structure of gp120 was also important for these properties. Constructs susceptible to antibody-mediated enhancement preferentially use CCR5 as a coreceptor, in contrast to constructs that were neutralized or not affected. Using monoclonal antibodies directed against CD4 or CCR5, we were able to show that antibody-mediated enhancement was CD4 dependent. Altogether, our results suggest that the modulation of the interaction of gp120 with CCR5 is the mechanism underlying antibody-mediated enhancement of HIV-1 infectivity.
|*Antibody-Dependent Enhancement, HIV Envelope Protein gp120/*chemistry/genetics/*metabolism, HIV Infections/virology, HIV-1/genetics/immunology/*pathogenicity, Humans, Neutralization Tests, Receptors, CCR5/*metabolism, Receptors, CXCR4/metabolism, Recombinant Fusion Proteins/genetics/metabolism, Research Support, Non-U.S. Gov't|
|Journal of Virology|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
Guillon, C, Schutten, M, Boers, P.H.M, Gruters, R.A, & Osterhaus, A.D.M.E. (2002). Antibody-mediated enhancement of human immunodeficiency virus type 1 infectivity is determined by the structure of gp120 and depends on modulation of the gp120-CCR5 interaction. Journal of Virology. Retrieved from http://hdl.handle.net/1765/9859