Tuesday, Dec 23, 2014

Low cholesterol in immune cells tied to slow HIV progression

The team reconstructed the epidemic's ancestral HIV sequence and from there, assessed the spread of immune escape mutations in the population. (Photo: Reuters) The team reconstructed the epidemic's ancestral HIV sequence and from there, assessed the spread of immune escape mutations in the population. (Photo: Reuters)
By: Press Trust of India | Washington | Posted: April 29, 2014 2:05 pm

People infected with HIV whose immune cells have low cholesterol levels experience much slower disease progression, even without medication, according to a new research. Researchers from the University of Pittsburgh Graduate School of Public Health found that low cholesterol in certain cells, which is likely an inherited trait, affects the ability of the body to transmit the virus to other cells.

When HIV enters the body, it is typically picked up by immune system cells called dendritic cells, which recognise foreign agents and transport the virus to lymph nodes where it is passed to other immune system cells, including T cells. HIV then uses T cells as its main site of replication. It is through this mechanism that levels of HIV increase and overwhelm the immune system, 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,” said lead author Giovanna Rappocciolo, an assistant professor at Pitt Public Health. “Instead the disease is much slower to progress, and we believe low cholesterol in dendritic cells may be a reason,” Rappocciolo said.

The discovery was made possible by using 30 years of data and biologic specimens collected through the Pitt Men’s Study, a confidential research study of the natural history of HIV/AIDS, part of the Multicenter AIDS Cohort Study (MACS). Through the Pitt Men’s Study/MACS, eight “nonprogressors” were assessed twice a year for an average of 11 years and compared to eight typically progressing HIV-positive counterparts.

Rappocciolo and her colleagues 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. None of the study participants were taking statins, which are cholesterol-lowering medications. 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,” said Rappocciolo. The study is published in mBio, the journal of the American Society for Microbiology.

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