Cholesterol metabolism in immune cells linked to HIV progression

Lower levels of cholesterol in certain immune cells – a result of enhanced cholesterol metabolism within those cells – may help explain why some HIV-infected people are able to naturally control disease progression.

The findings provide a basis for potential development of new approaches to control HIV infection by regulating cellular cholesterol metabolism.

Immune cells known as antigen-presenting cells (APCs) can take up HIV particles and deliver intact, infectious virus to its primary target – T cells – through a replication-independent process known as trans infection. Scientists funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the US National Institutes of Health (NIH), found that APCs from non-progressors – HIV-infected people whose disease does not progress for many years even without antiretroviral therapy – do not effectively trans infect T cells. A closer look revealed that this defect in trans infection is likely due to enhanced cholesterol metabolism within the non-progressors’ APCs, which appears to be an inherited trait.

Research findings may contribute to new approaches to manage HIV infection

These observations came from analysis of data and samples provided by participants in the NIH-supported Multicentre AIDS Cohort Study (MACS).

To identify genetic factors linked to defective trans infection, Giovanna Rappocciolo, Ph.D., of the University of Pittsburgh and colleagues searched for patterns in gene expression, or the degree to which specific genes are turned on or off, in APCs from eight HIV non-progressors and eight progressors enrolled in MACS. Compared to APCs from progressors, cells from non-progressors expressed higher levels of several cholesterol-related genes associated with defective trans infection. These results improve understanding of how non-progressors control HIV without drug therapy and potentially may contribute to new approaches to manage HIV infection.

The research findings will be presented in a poster at the 8th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2015) in Vancouver, Canada.