Maturation-Induced Cloaking of Neutralization Epitopes on HIV-1 Particles

PLoS Pathogens

Jordan R. Willis¹  James E. Crowe Jr.²  Amanda S. Joyner²  Christopher Aiken³ 

[1] Chemical and Physical Biology Program, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America;Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America;Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America

关键词: HIV-1;    Virions;    Antibodies;    Binding analysis;    Cell fusion;    Enzyme-linked immunoassays;    Cell binding;    Immune evasion;   

DOI  :  10.1371/journal.ppat.1002234

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

To become infectious, HIV-1 particles undergo a maturation process involving proteolytic cleavage of the Gag and Gag-Pol polyproteins. Immature particles contain a highly stable spherical Gag lattice and are impaired for fusion with target cells. The fusion impairment is relieved by truncation of the gp41 cytoplasmic tail (CT), indicating that an interaction between the immature viral core and gp41 within the particle represses HIV-1 fusion by an unknown mechanism. We hypothesized that the conformation of Env on the viral surface is regulated allosterically by interactions with the HIV-1 core during particle maturation. To test this, we quantified the binding of a panel of monoclonal antibodies to mature and immature HIV-1 particles by immunofluorescence imaging. Surprisingly, immature particles exhibited markedly enhanced binding of several gp41-specific antibodies, including two that recognize the membrane proximal external region (MPER) and neutralize diverse HIV-1 strains. Several of the differences in epitope exposure on mature and immature particles were abolished by truncation of the gp41 CT, thus linking the immature HIV-1 fusion defect with altered Env conformation. Our results suggest that perturbation of fusion-dependent Env conformational changes contributes to the impaired fusion of immature particles. Masking of neutralization-sensitive epitopes during particle maturation may contribute to HIV-1 immune evasion and has practical implications for vaccine strategies targeting the gp41 MPER.

【 授权许可】

CC BY