Elite suppressor-derived HIV-1 envelope glycoproteins exhibit reduced entry efficiency and kinetics

• Published in: PLoS pathogens Vol. 5; no. 4; p. e1000377
• Main Authors: Lassen, Kara G, Lobritz, Michael A, Bailey, Justin R, Johnston, Samantha, Nguyen, Sandra, Lee, Benhur, Chou, Tom, Siliciano, Robert F, Markowitz, Martin, Arts, Eric J
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.04.2009; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; AIDS; Blotting, Western; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - virology; Charitable foundations; Cloning; Development and progression; Disease; Drug therapy; Efficiency; Experiments; Flow Cytometry; Gene Products, env - immunology; Genetic diversity; Grants; HIV; HIV infection; HIV Infections - immunology; HIV Infections - virology; HIV-1 - pathogenicity; Human immunodeficiency virus; Humans; Infectious Diseases/HIV Infection and AIDS; Physiological aspects; Plasma; Properties; Receptors; Receptors, CCR5 - immunology; Reverse Transcriptase Polymerase Chain Reaction; Viral Load; Viral proteins; Virology/Immunodeficiency Viruses; Virology/Mechanisms of Resistance and Susceptibility, including Host Genetics; Virus Internalization; Viruses; United States; HIV Infections; HIV-1; Flow Cytometry; Humans; Receptors, CCR5; CD4-Positive T-Lymphocytes; Gene Products, env; Reverse Transcriptase Polymerase Chain Reaction; Blotting, Western; Viral Load; Virus Internalization
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1000377

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.