Elite Suppressor–Derived HIV-1 Envelope Glycoproteins Exhibit Reduced Entry Efficiency and Kinetics

PLoS Pathogens

Samantha Johnston¹  Martin Markowitz¹  Tom Chou²  Benhur Lee²  Sandra Nguyen²  Michael A. Lobritz³  Kara G. Lassen³  Robert F. Siliciano⁴  Justin R. Bailey⁵  Eric J. Arts⁶ 

[1] Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America;Department of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, California, United States of America;Department of Molecular Biology and Microbiology, Department of Medicine, Case Western Reserve University, Cleveland, Ohio, United States of America;Departments of Biomathematics and Mathematics, University of California Los Angeles, Los Angeles, California, United States of America;Division of Infectious Diseases, Department of Medicine, Case Western Reserve University, Cleveland, Ohio, United States of America;Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America

关键词: Cloning;    HIV-1;    Viral replication;    CCR5 coreceptor;    CD coreceptors;    Cell fusion;    Luciferase;    Reverse transcription;   

DOI  :  10.1371/journal.ppat.1000377

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Elite suppressors (ES) are a rare subset of HIV-1–infected individuals who are able to maintain HIV-1 viral loads below the limit of detection by ultra-sensitive clinical assays in the absence of antiretroviral therapy. Mechanism(s) responsible for this elite control are poorly understood but likely involve both host and viral factors. This study assesses ES plasma-derived envelope glycoprotein (env) fitness as a function of entry efficiency as a possible contributor to viral suppression. Fitness of virus entry was first evaluated using a novel inducible cell line with controlled surface expression levels of CD4 (receptor) and CCR5 (co-receptor). In the context of physiologic CCR5 and CD4 surface densities, ES envs exhibited significantly decreased entry efficiency relative to chronically infected viremic progressors. ES envs also demonstrated slow entry kinetics indicating the presence of virus with reduced entry fitness. Overall, ES env clones were less efficient at mediating entry than chronic progressor envs. Interestingly, acute infection envs exhibited an intermediate phenotypic pattern not distinctly different from ES or chronic progressor envs. These results imply that lower env fitness may be established early and may directly contribute to viral suppression in ES individuals.

【 授权许可】

CC BY