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
The Secret of the Rock Drawings
24.05.2019 | Max-Planck-Institut für Chemie
Chemical juggling with three particles
24.05.2019 | Rheinische Friedrich-Wilhelms-Universität Bonn
A new assessment of NASA's record of global temperatures revealed that the agency's estimate of Earth's long-term temperature rise in recent decades is accurate to within less than a tenth of a degree Fahrenheit, providing confidence that past and future research is correctly capturing rising surface temperatures.
The most complete assessment ever of statistical uncertainty within the GISS Surface Temperature Analysis (GISTEMP) data product shows that the annual values...
Physicists at the University of Basel are able to show for the first time how a single electron looks in an artificial atom. A newly developed method enables them to show the probability of an electron being present in a space. This allows improved control of electron spins, which could serve as the smallest information unit in a future quantum computer. The experiments were published in Physical Review Letters and the related theory in Physical Review B.
The spin of an electron is a promising candidate for use as the smallest information unit (qubit) of a quantum computer. Controlling and switching this spin or...
Engineers at the University of Tokyo continually pioneer new ways to improve battery technology. Professor Atsuo Yamada and his team recently developed a...
With a quantum coprocessor in the cloud, physicists from Innsbruck, Austria, open the door to the simulation of previously unsolvable problems in chemistry, materials research or high-energy physics. The research groups led by Rainer Blatt and Peter Zoller report in the journal Nature how they simulated particle physics phenomena on 20 quantum bits and how the quantum simulator self-verified the result for the first time.
Many scientists are currently working on investigating how quantum advantage can be exploited on hardware already available today. Three years ago, physicists...
'Quantum technologies' utilise the unique phenomena of quantum superposition and entanglement to encode and process information, with potentially profound benefits to a wide range of information technologies from communications to sensing and computing.
However a major challenge in developing these technologies is that the quantum phenomena are very fragile, and only a handful of physical systems have been...
29.04.2019 | Event News
17.04.2019 | Event News
15.04.2019 | Event News
24.05.2019 | Physics and Astronomy
24.05.2019 | Medical Engineering
24.05.2019 | Life Sciences