In this context, the protein SAMHD1 plays a key role. In addition, the investigators were able to show by means of blood samples from patients with a rare congenital disease that the absence of SAMHD1 makes early detection of the virus possible via the immune system. PLoS Pathogens reports on the research results in its online issue of December 8, 2012 (CET: December 9, 2012, 01.00)
Monocytes infected with HIV-1 (yellow-green) and non-infected monocytes (red). The cells originate from patients with the rare Aicardi-Goutières syndrome and were infected in cell culture. These cells do not have a functioning SAMHD1 and can therefore be infected by HIV-1.
Image credit: Prof. Viviana Simon, Department of Microbiology, Mount Sinai School of Medicine, New York
The generally feared human immunodeficiency virus very efficiently infects T lymphocytes, a special cell group of the immune system, in the human organism. On the other hand, myeloid blood cells, such as dendritic cells, monocytes, and partly macrophages, which also serve to support immune responses, provide natural protection against HIV-1. Researchers at the Paul-Ehrlich-Institut (PEI) under the supervision of Dr Egbert Flory, head of the section "Tissue Engineering and Somatic cell therapeutics" in the Division Medical Biotechnology and research group leader Professor Renate König have now proved that the cellular protein SAMHD1 ("SAM domain and HD domain containing protein 1") is responsible if monocytes are not infected by the human immunodeficiency virus.
This 'protective function' of SAMHD1 can, however, be switched off in the non-infectable cells, if viral protein X (Vpx) is inserted into the cells, as the scientists at the PEI were able to show. Vpx interacts with SAMHD1 which causes the latter to disintegrate. As a result, the previously HIV-1-resistant cells become infectable. In further experiments, the researchers used a mutated Vpx variant. This variant is no longer able to bind to SAMHD1 and is thus no longer able to induce disintegration of the protein. In these experiments, no infection developed. These experiments support previously published findings of two other research teams who described the significance of SAMHD2 as restrictive factor in an HIV-1-infection for dendritic cells and macrophages.
The researchers of the PEI went one step further: In collaboration with Professor Frank Rutsch, University Hospital Münster, and researchers of the Mount Sinai School of Medicine at New York under the supervision of Professor Viviana Simon and Professor Ana Fernandez-Sesma, they investigated how monocytes of patients with the very rare Aicardi-Goutières syndrome reacted to the human immunodeficiency virus.
Due to a mutation, the cells of the patient suffering from this serious congenital disease lack the functional SMHD1 protein: "While monocytes normally cannot be infected by HIV at all, these cells revealed massive replication of the virus. A very important finding, above all, is that, here too, a first early response of the immune cells to the virus was recognisable", explained Dr König. While in the case of influenza viruses, a rapid first immune response of the infected cells is induced with interferon release, because the viral RNA is recognised as foreign when entering the cell, the immunodeficiency virus escapes this early response phase unnoticed.
"This finding is of great significance for the development of vaccines against HIV infections", emphasised Professor Klaus Cichutek, president of the PEI. "Previous investigations have been of little success because no suitable immune response was induced by the potential vaccine candidates. Understanding the early camouflage mechanism of the virus may help us identify new approaches to finding a better immune response". In addition, with SAMHD1, an important key to a system has been found which protects cells from an HIV infection.
Dr. Susanne Stöcker | idw
'Y' a protein unicorn might matter in glaucoma
23.10.2017 | Georgia Institute of Technology
Microfluidics probe 'cholesterol' of the oil industry
23.10.2017 | Rice University
Salmonellae are dangerous pathogens that enter the body via contaminated food and can cause severe infections. But these bacteria are also known to target...
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
23.10.2017 | Event News
17.10.2017 | Event News
10.10.2017 | Event News
23.10.2017 | Life Sciences
23.10.2017 | Physics and Astronomy
23.10.2017 | Health and Medicine