Low cholesterol in immune cells changes the body’s ability to transmit the virus to other cells, scientists say. Having low cholesterol in certain cells is likely an inherited trait, but it could point to new ways to fight HIV.
When someone is infected with HIV, the virus is picked up by immune system cells called dendritic cells. Ultimately the virus is passed on to T cells, which HIV uses to replicate.
This allows the virus to eventually overwhelm the immune system, which leads to AIDS.
Some people with the virus do not experience the loss of T cells and the rapid increase in HIV. They can sometimes go many years, even more than a decade, without the virus seriously compromising the immune system or leading to AIDS.
“We’ve known for two decades that some people don’t have the dramatic loss in their T cells and progression to AIDS that you’d expect without drug therapy,” says Giovanna Rappocciolo, an assistant professor at the University of Pittsburgh Graduate School of Public Health. “Instead the disease is much slower to progress, and we believe low cholesterol in dendritic cells may be a reason.”
Cholesterol levels in cells, not bloodRappocciolo and colleagues assessed eight such “nonprogressors” twice a year for an average of 11 years and compared them to eight typically progressing HIV-positive counterparts.
They found that in nonprogressors, the dendritic cells were not transferring the virus to T cells at detectible levels. When taking a closer look at these dendritic cells, the researchers discovered that the cells had low levels of cholesterol, even though the nonprogressors had regular levels of cholesterol in their blood.A similar finding was shown for B lymphocytes, which also pass HIV to T cells, leading to high rates of HIV replication.
Cholesterol is an essential component of the outer membranes of cells. It is required for HIV to replicate efficiently in different types of cells. None of the study participants were taking statins, which are cholesterol-lowering medications that some people take to prevent vascular problems when cholesterol in their blood is too high.
When HIV was directly mixed with the nonprogressors’ T cells in the laboratory, those T cells became infected with the virus at the same rate as the T cells of the regularly progressing, HIV-positive participants. Indeed, T cells from the nonprogressors had normal levels of cholesterol.
“This means that the disruption is unlikely to be due to a problem with the T cells, further supporting our conclusion that the slow progression is linked to low cholesterol in the dendritic cells and B cells,” says Rappocciolo.
“What is most intriguing is that dendritic cells in the nonprogressors had this protective trait years before they became infected with HIV,” says Charles Rinaldo, chair of the infectious diseases and microbiology department and professor of pathology. “This strongly suggests that the inability of their dendritic cells and B cells to pass HIV to their T cells is a protective trait genetically inherited by a small percentage of people.
“Understanding how this works could be an important clue in developing new approaches to prevent progression of HIV infection.”
The National Institutes of Health supported the study, which is published in the journal mBio.
Source: University of Pittsburgh
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HIV cell photo from Niaid/Flickr