"In [infected] primary human tonsils and spleens, there is a profound depletion of CD4 T cells," said Warner Greene of The Gladstone institute for Virology and Immunology in San Francisco. "In tonsils, only one to five percent of those cells are directly infected, yet 99 percent of them die."
Lymphoid tissues, including tonsils and spleen, contain the vast majority of the body's CD4 T cells and represent the major site where HIV reproduces itself. And it now appears that those dying T cells aren't bystanders exactly.
The HIV virus apparently does invade those T cells, but the cells somehow block virus replication. It is the byproducts of that aborted infection that trigger an immune response that is ultimately responsible for killing those cells.
More specifically, when the virus enters the CD4 T cells that will later die, it begins to copy its RNA into DNA, Greene and his colleague Gilad Doitsh explain. That process, called reverse transcription, is what normally allows a virus to hijack the machinery of its host cell and begin replicating itself. But in the majority of those cells, the new findings show that the process doesn't come to completion.
The cells sense partial DNA transcripts as they accumulate and, in a misguided attempt to protect the body, commit a form of suicide. Greene says that completed viral transcripts in cells that are productively infected probably don't provoke the same reaction because they are so rapidly shuttled into the nucleus and integrated into the host's own DNA.
The researchers narrowed down the precise "death window" of those so-called bystander cells by taking advantage of an array of HIV drugs that act at different points in the viral life cycle. Drugs that blocked viral entry or that prevented reverse transcription altogether stopped the CD4 T cell killing, they report. Those drugs that act later in the life cycle to prevent reverse transcription only after it has already begun did not save the cells from their death.
Those cells don't die quietly either, Greene says. The cells produce ingredients that are the hallmarks of inflammation and break open, spilling all of their contents. That may provide a missing link between HIV and the inflammation that tends to go with it.
"That inflammation will attract more cells leading to more infection," Greene said. "It's a vicious cycle."
The findings also show that the CD4 T cells' demise is a response designed to be protective of the host. All that goes awry in the case of HIV and "the CD4 T cells just get blown away," compromising the immune system.
Greene said that all the available varieties of anti-HIV drugs will still work to fight the infection by preventing the virus from spreading and reducing the viral load.
The findings may lead to some new treatment strategies, however. For instance, it may be possible to develop drugs that would act on the cell sensor that triggers the immune response, helping to prevent the loss of CD 4 T cells. His team plans to explore the identity of that sensor in further studies. They also are interested to find out if the virus has strategies in place to try and prevent the CD4 T cells' death.
"The cell death pathway is really not in the virus's best interest," Greene says. "It precludes the virus from replicating and the virus may have ways to repel it."
Elisabeth Lyons | EurekAlert!
Rutgers scientists discover 'Legos of life'
23.01.2018 | Rutgers University
Researchers identify a protein that keeps metastatic breast cancer cells dormant
23.01.2018 | Institute for Research in Biomedicine (IRB Barcelona)
Physicists have developed a technique based on optical microscopy that can be used to create images of atoms on the nanoscale. In particular, the new method allows the imaging of quantum dots in a semiconductor chip. Together with colleagues from the University of Bochum, scientists from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute reported the findings in the journal Nature Photonics.
Microscopes allow us to see structures that are otherwise invisible to the human eye. However, conventional optical microscopes cannot be used to image...
On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.
We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...
What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...
For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.
Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...
At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.
No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...
08.01.2018 | Event News
11.12.2017 | Event News
08.12.2017 | Event News
23.01.2018 | Life Sciences
23.01.2018 | Earth Sciences
23.01.2018 | Physics and Astronomy