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

Kara G. Lassen, Michael A. Lobritz, Justin Bailey, Samantha Johnston, Sandra Nguyen, Benhur Lee, Tom Chou, Robert F Siliciano, Martin Markowitz, Eric J. Arts

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalPLoS Pathogens
Volume5
Issue number4
DOIs
StatePublished - Apr 2009

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HIV-1
Glycoproteins
CCR5 Receptors
env Gene Products
Virus Internalization
CD4 Antigens
Viral Load
Limit of Detection
Clone Cells
Viruses
Cell Line
Infection
Therapeutics

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Elite suppressor-derived hiv-1 envelope glycoproteins exhibit reduced entry efficiency and kinetics. / Lassen, Kara G.; Lobritz, Michael A.; Bailey, Justin; Johnston, Samantha; Nguyen, Sandra; Lee, Benhur; Chou, Tom; Siliciano, Robert F; Markowitz, Martin; Arts, Eric J.

In: PLoS Pathogens, Vol. 5, No. 4, 04.2009.

Research output: Contribution to journalArticle

Lassen, Kara G. ; Lobritz, Michael A. ; Bailey, Justin ; Johnston, Samantha ; Nguyen, Sandra ; Lee, Benhur ; Chou, Tom ; Siliciano, Robert F ; Markowitz, Martin ; Arts, Eric J. / Elite suppressor-derived hiv-1 envelope glycoproteins exhibit reduced entry efficiency and kinetics. In: PLoS Pathogens. 2009 ; Vol. 5, No. 4.
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