Elite suppressor-derived HIV-1 envelope glycoproteins

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

Elite suppressors 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 elite suppressors 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, elite supressors envs exhibited significantly decreased entry efficiency relative to chronically infected viremic progressors. Elite suppressors envs also demonstrated slow entry kinetics indicating the presence of virus with reduced entry fitness. Overall, elite suppressors 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 elite suppressors or chronic progressor envs. These results imply that lower env fitness may be established early and may directly contribute to viral suppression in elite suppressors individuals.

Editors’ note: This study is the first to provide direct evidence that the envelope glycoprotein, the coat protein of HIV, in elite suppressors is less efficient in supporting HIV entry into host cells that that of HIV found in people with disease progression. In acute infection, there are HIV variants with a wide range of efficiencies, suggesting that elite suppressors may be selecting relatively lower fitness env variants right at the start. How they would do this remains a mystery, as no data exist on the natural history of acute infection in elite suppressors.C