A novel discovery by researchers at NYU Langone Medical Center and colleagues reveals a mechanism by which the immune system tries to halt the spread of HIV. Harnessing this mechanism may open up new paths for therapeutic research aimed at slowing the virus' progression to AIDS. The study appears online ahead of print today in Nature Immunology.
"A lot of research on viruses, especially HIV, is aimed at trying to understand what the body's mechanisms of resistance are and then to understand how the virus has gotten around these mechanisms," said co-lead investigator Nathaniel R. Landau, PhD, a professor of microbiology at the Joan and Joel Smilow Research Center at NYU School of Medicine.
The research focused on a protein called SAMHD1. Recent studies have found that immune cells, called dendritic cells, containing the protein are resistant to infection by HIV. Since the discovery, scientists have sought to understand how SAMHD1 works to protect these cells, with hopes that science might find a way to synthetically apply that protection to other cells.
Dr. Landau and his team are now able to provide an answer:
When a virus, like HIV, infects a cell, it hijacks the cell's molecular material to replicate. That molecular material is in the form of deoxynucleotide triphosphates (dNTPs), which are the building blocks for DNA. Once the virus replicates, the resulting DNA molecule contains all the genes of the virus and instructs the cell to make more virus.
Researchers wanted to understand how cells containing the SAMHD1 protein are protected from such hijacking. They found that SAMHD1 protects the cell from viruses by destroying the pool of dNTPs, leaving the virus without any building blocks to make its genetic information – a process researchers call nucleotide pool depletion. "SAMHD1 essentially starves the virus," Dr. Landau said. "The virus enters the cell and then nothing happens. It has nothing to build and replicate with, so no DNA is made."
As a result, the most common form of HIV does not readily infect these cells. Instead, the virus has evolved to replicate mainly in a different kind of cell, called CD4 T-cells, which do not contain SAMHD1 and therefore have a healthy pool of dNTPs. Dr. Landau explained that the virus has evolved in such a way that it may deliberately avoid trying to infect immune cells with SAMHD1 to avoid alerting the greater immune system to activate a variety of antiviral mechanisms to attack the virus. Viruses that are related to HIV, like HIV-2 and SIV, have developed a protein called viral protein X (VPX) that directly attacks SAMHD1. This allows the virus to infect dendritic cells, an important type of immune cell.
"Viruses are remarkably clever about evading our immune defenses," Dr. Landau said. "They can evolve quickly and have developed ways to get around the systems we naturally have in place to protect us. It's a bit of evolutionary warfare and the viruses, unfortunately, usually win. We want to understand how the enemy fights so that we can outsmart it in the end."
Understanding the mechanism by which SAMHD1 provides protection to cells may provide a new idea about how to stop or slow the virus' ability to spread, Dr. Landau explained. Potential future research efforts, for example, might focus on finding a way to increase the amount of SAMHD1 in cells where it does not exist, or to reduce the amount of dNTPs in cells vulnerable to infection.
"Over the past few years, a number of these natural resistance mechanisms have been identified, specifically in HIV, but some have potential applications to other viruses, as well," he said. "This is a very exciting time in HIV research. Many of the virus' secrets are being revealed through molecular biology, and we're learning a tremendous amount about how our immune system works through the study of HIV."
Funded in part by the National Institutes of Health and the American Foundation for AIDS Research, the study was conducted in collaboration with researchers at several institutions, including the University of Rochester Medical Center and The Cochin Institute, in Paris.
About NYU School of Medicine:
NYU School of Medicine is one of the nation's preeminent academic institutions dedicated to achieving world class medical educational excellence. For 170 years, NYU School of Medicine has trained thousands of physicians and scientists who have helped to shape the course of medical history and enrich the lives of countless people. An integral part of NYU Langone Medical Center, the School of Medicine at its core is committed to improving the human condition through medical education, scientific research and direct patient care. The School also maintains academic affiliations with area hospitals, including Bellevue Hospital, one of the nation's finest municipal hospitals where its students, residents and faculty provide the clinical and emergency care to New York City's diverse population, which enhances the scope and quality of their medical education and training. Additional information about the NYU School of Medicine is available at http://school.med.nyu.edu/.
Jessica Guenzel | 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