HIV infection can damage bystander cells

Washington: A recent study found that HIV-infected cells release vesicles that contain a viral protein called Nef, further damaging cholesterol metabolism and triggering inflammation in uninfected bystander cells.

HIV infects only a limited repertoire of cells expressing HIV receptors. But HIV infection is also associated with conditions involving the dysfunction of cells that cannot be infected by HIV, such as hardening of the arteries, dementia, kidney impairment, and certain heart problems.

These HIV-associated conditions persist even after the successful application of antiretroviral therapy when no virus is found in the blood. Many of these conditions involve impairments in cholesterol metabolism. In the new study published in the journal of PLOS Pathogens, researchers examined the mechanisms that may contribute to HIV-associated metabolic conditions.

The results showed that the HIV protein Nef is released from infected cells in vesicles that are then rapidly taken up by uninfected bystander white blood cells, impairing cholesterol metabolism in these cells.

This impairment caused the formation of excessive lipid rafts discrete lipid domains present in the external leaflet of the plasma membrane and the re-localisation of inflammatory receptors into rafts, triggering inflammation. The findings demonstrate how a single viral molecule released from infected cells into circulation may contribute to a range of pathogenic responses.

"Our study points to a common mechanism of various co-morbidities of HIV infection. This opens a possibility to target this mechanism using drugs affecting cholesterol metabolism to treat several comorbidities in people living with HIV," said one of the researchers of the study, Dmitri Sviridov.