Low cholesterol in immune cells slows HIV progression

Why some HIV-infected people experience much slower disease progression, even without medication? It has to do with cholesterol levels in specific immune cells, scientists have found.

"A fascinating aspect of the AIDS epidemic is that a small percentage of HIV-1-infected persons maintain a relatively normal number of CD4 T cells (Th cells) and low viral load for many years without receiving antiviral therapy," said Giovanna Rappocciolo from University of Pittsburgh. 

Knowing how these individuals naturally control their HIV-1 infection and prevent the virus from progressively destroying their Th cells could be critically important to developing effective therapeutic and prevention strategies for HIV-1/AIDS, she added.

When HIV enters the body, it is typically picked up by immune system cells, called antigen-presenting cells (APCs), including dendritic cells and B lymphocytes. 

Those cells then transport the virus to lymph nodes where the APCs pass it to other immune system cells, including Th cells, via a process known as trans infection. 

HIV then uses Th cells as its main site of replication.
"It is through replication in the Th cells that levels of HIV increase and overwhelm the immune system," she noted.

In the study Rappocciolo and her colleagues compared the ability of APCs from nonprogessors, progressors and uninfected control subjects to trans infect T cells.


They found that while the cells from progression and control subjects were highly effective at mediating trans infection, those from non-progression lacked the ability.

The researchers took a closer look and discovered that the APCs from non-progression had low levels of cholesterol, even though the patients had regular levels of cholesterol in their blood. 

This defect in cholesterol metabolism is not a direct consequence of virus infection. 

Rather, it is likely present as an inherited trait in a low percentage of individuals.


"Understanding how this works could be an important clue in developing new approaches to prevent progression of HIV infection," Rappocciolo said.

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