News » Research Team Publishes Study on Role of HIV Protein in Metabolic Comorbidities

Research Team Publishes Study on Role of HIV Protein in Metabolic Comorbidities

A research team including Michael Bukrinsky, MD, PhD, professor of microbiology, immunology, and tropical medicine at the George Washington University School of Medicine and Health Sciences, found that HIV protein Nef plays a role in causing inflammation and other HIV-associated metabolic comorbidities. The findings were published in the journal PLOS Pathogens.

“HIV infects a limited repertoire of cells expressing HIV receptors,” said Bukrinsky, who served as senior author of the study. “Comorbidities of HIV infection, such as atherosclerosis, dementia, and renal impairment, involve dysfunction of cells that cannot be infected by HIV. These comorbidities can persist even after application of antiretroviral therapies when no trace of a virus is found in the blood. We believe these comorbidities are caused by continuous release of HIV proteins from a small number of persistently infected cells.”

The researchers found that HIV protein Nef released by infected cells in extracellular vesicles is taken up by “bystander” cells, or cells that are uninfected, impairing cholesterol metabolism in these cells. The impairment leads to the formation of excessive lipid rafts, which are subdomains of the plasma membrane that contain high concentrations of cholesterol and glycosphingolipids; re-localization of the inflammatory receptors into the rafts; and triggered inflammation.

“Our work demonstrates how a single viral factor released from infected cells into circulation may cause pathogenic responses,” Bukrinsky said. “These mechanisms may contribute to HIV-associated metabolic comorbidities.”

The research team suggests that, through the production of lipid rafts and the resulting inflammation, HIV protein Nef contributes to atherosclerosis and HIV-associated neurocognitive disorder, among several other comorbidities.

To read the study, titled “Exomsomes containing HIV protein Nef reorganize lipid rafts potentiating inflammatory response in bystander cells,” published in PLOS Pathogens, visit www.ncbi.nlm.nih.gov/pmc/articles/PMC6657916/.