Low cholesterol in immune cells tied to slow progression of HIV

April 29, 2014
University of Pittsburgh Graduate School of Public Health researchers have shown that low cholesterol in dendritic cells might be the reason that HIV progression to AIDS is naturally slowed in some people. Credit: Nicole Davison/UPMC

People infected with HIV whose immune cells have low cholesterol levels experience much slower disease progression, even without medication, according to University of Pittsburgh Graduate School of Public Health research that could lead to new strategies to control infection.

The Pitt Public Health researchers found that in certain cells, which is likely an inherited trait, affects the ability of the body to transmit the virus to other cells. The discovery, funded by the National Institutes of Health (NIH), is featured in today's issue of mBio, the journal of the American Society for Microbiology.

When HIV enters the body, it is typically picked up by called , which recognize 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. Once a person develops AIDS, the body can no longer fight infections and cancers. Prior to effective drug therapy, the person died within one to two years after the AIDS diagnosis.

"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, Ph.D., 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."

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 national NIH-funded Multicenter AIDS Cohort Study (MACS).

"We couldn't have made this discovery without the MACS. Results like ours are the real pay-off of the past three decades of meticulous data and specimen collection," said senior author Charles Rinaldo, Ph.D., chairman of Pitt Public Health's Department of Infectious Diseases and Microbiology, and professor of pathology. "It is thanks to our dedicated volunteer participants that we are making such important advances in understanding HIV, and applying it to preventing and treating AIDS."

Medications called combination antiretroviral therapy (ART) disrupt the viral replication process and can delay the onset of AIDS by decades.

However, even without taking ART, a small percentage of people infected with HIV do not have the persistent loss of T cells and increase in levels of HIV after initial infection. They can sometimes go many years, even more than a decade, without the virus seriously compromising the or leading to AIDS.

Through the Pitt Men's Study/MACS, eight such "nonprogressors" were assessed twice a year for an average of 11 years and compared to eight typically progressing HIV-positive counterparts.

Dr. 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.

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," said Dr. Rappocciolo.

"What is most intriguing is that dendritic cells in the nonprogressors had this protective trait years before they became infected with HIV," Dr. Rinaldo said. "This strongly suggests that the inability of their dendritic cells and B cells to pass HIV to their T 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."

Explore further: Scientists find the invisibility cloak that shields HIV-1 from the immune system

Related Stories

Scientists find the invisibility cloak that shields HIV-1 from the immune system

November 21, 2013
Of the two major types of HIV, only one, HIV-1, typically causes AIDS in infected people who don't receive treatment. A study published by Cell Press November 21st in the journal Immunity reveals how HIV-1 escapes detection ...

NIH study describes new method for tracking T cells in HIV patients

February 3, 2014
A team of researchers has reported a novel method for tracking CD4+ T cells in people infected with HIV. CD4+ T cells are critical for immune defense against an array of pathogens and are a primary target of HIV. In the study, ...

Researchers find immune cells may play previously unrecognized role in inflammation in HIV/AIDS

May 29, 2013
(Medical Xpress)—Depleted numbers of a specific type of white blood cell in the immune systems of people infected with HIV/AIDS appear to be associated with increased levels of unchecked and often damaging inflammation ...

Harnessing immune cells' adaptability to design an effective HIV vaccine

March 21, 2013
In infected individuals, HIV mutates rapidly to escape recognition by immune cells. This process of continuous evolution is the main obstacle to natural immunity and the development of an effective vaccine. A new study published ...

New target to fight HIV infection identified

October 1, 2013
A mutant of an immune cell protein called ADAP (adhesion and degranulation-promoting adaptor protein) is able to block infection by HIV-1 (human immunodeficiency virus 1), new University of Cambridge research reveals. The ...

Viral replication may not be primary cause of HIV-1 persistence in patients receiving cART

November 26, 2013
(Medical Xpress)—A team of researchers with members from Europe and the U.S. has found that viral replication may not be the main reason that the HIV virus is able to persist in the cells of infected patients for many years. ...

Recommended for you

Paris spotlight on latest in AIDS science

July 21, 2017
Some 6,000 HIV experts gather in Paris from Sunday to report advances in AIDS science as fading hopes of finding a cure push research into new fields.

Scientists elicit broadly neutralizing antibodies to HIV in calves

July 20, 2017
Scientists supported by the National Institutes of Health have achieved a significant step forward, eliciting broadly neutralizing antibodies (bNAbs) to HIV by immunizing calves. The findings offer insights for HIV vaccine ...

Heart toxin reveals new insights into HIV-1 integration in T cell genome

July 20, 2017
Human immunodeficiency virus (HIV)-1 may have evolved to integrate its genetic material into certain immune-cell-activating genes in humans, according to new research published in PLOS Pathogens.

Scientists capture first high-resolution image of key HIV protein transitional state

July 13, 2017
A new, three-dimensional snapshot of HIV demonstrates the radical structural transformations that enable the virus to recognize and infect host cells, according to a new study led by scientists at The Scripps Research Institute ...

Barrier to autoimmune disease may open door to HIV, study suggests

July 11, 2017
Researchers from the University of Colorado School of Medicine have discovered that a process that protects the body from autoimmune disease also prevents the immune system from generating antibodies that can neutralize the ...

Team tests best delivery mode for potential HIV vaccine

June 20, 2017
For decades, HIV has successfully evaded all efforts to create an effective vaccine but researchers at The Scripps Research Institute (TSRI) and the La Jolla Institute for Allergy and Immunology (LJI) are steadily inching ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.