Deciphering how CD4 T cells die during HIV infection

Nov 24, 2010

Scientists at Gladstone Institute of Virology and Immunology have solved a long-standing mystery about HIV infection–namely how HIV promotes the death of CD4 T cells. It is the loss of this critical subset of immune cells that leads to the development of AIDS. Most immune cells that die during HIV infection are seemingly not infected, a phenomenon formerly described as "bystander cell killing." Now the Gladstone scientists report that these "bystander" cells are actually the victims of a failed or abortive form of viral infection. Their findings are published in today's issue of the journal Cell.

Dr. Gilad Doitsh, who performed many of the studies and is the lead author of the paper stated, "Our study reveals that the virus actually enters the CD4 T that are destined to die and that the virus starts to make a DNA copy of its RNA, a process called reverse transcription. However, this process does not work well in the majority of these cells and the incomplete DNA intermediates that accumulate in the cytoplasm are sensed and trigger the cells to 'commit suicide' in an attempt to protect the body."

The researchers identified the precise step in which the CD4 T cells die by using different anti-HIV drugs to arrest the virus at different points in its life cycle. Drugs that blocked viral entry or that blocked the start of reverse transcription stopped the killing. Conversely, drugs that acted later in the life cycle did not. Importantly, the researchers used primary human lymphoid tissues, such as tonsil and spleen to uncover this death pathway. These and other lymphoid tissues contain over 98% of the body's CD4 T cells and represent the major site where the virus reproduces itself.

The team also found that the dying cells do not go silently into the night. As they die, these cells release proteins, called cytokines, that cause inflammation and that attract healthy cellular targets promoting repeated rounds of infection and cell death. Scientists have long been interested in why infection and inflammation seem to go hand in hand. This study reveals a new mechanism linking the virus to inflammation.

"Our findings have revealed a completely unexpected mechanism for CD4 T-cell death during HIV infection" said Warner C. Greene, institute director and senior author of the paper. "These results highlight how a natural cellular defense normally used by the host to repel foreign invaders goes awry in , resulting in a profound depletion of CD4 T cells. If untreated, this process ultimately causes AIDS."

Explore further: Prions can trigger 'stuck' wine fermentations, researchers find

Related Stories

AIDS resistance secret may be in blood

Feb 12, 2007

U.S. scientists say the absence of a specific marker in the blood and tissues of certain monkeys might be part of the key to understanding AIDS resistance.

Asthma risk increases in children treated for HIV

Jul 01, 2008

Children whose immune systems rebound after treatment with potent anti-viral drugs for HIV infection face an increased risk of developing asthma, said a federally funded consortium of researchers led by those from Baylor ...

HIV measurement is questioned

Sep 27, 2006

Preliminary U.S. research indicates the HIV RNA level in untreated HIV-infected patients has little value in predicting the rate of CD4 cell count decrease.

Scientists identify new cellular receptor for HIV

Feb 10, 2008

A cellular protein that helps guide immune cells to the gut has been newly identified as a target of HIV when the virus begins its assault on the body's immune system, according to researchers from the National Institute ...

A reductionist approach to HIV research

Nov 30, 2009

A major obstacle to HIV research is the virus's exquisite specialisation for its human host - meaning that scientists' traditional tools, like the humble lab mouse, can deliver only limited information. Now, a team of researchers ...

Recommended for you

New tool aids stem cell engineering for medical research

22 hours ago

A Mayo Clinic researcher and his collaborators have developed an online analytic tool that will speed up and enhance the process of re-engineering cells for biomedical investigation. CellNet is a free-use Internet platform ...

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

junkd
not rated yet Nov 28, 2010
Reliable supplier, rapid delivery, guarantee!
http://star-of-he..._id=5831