Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Appearance of HIV in the early warning system – camouflage uncovered

09.12.2011
While the human immunodeficiency virus replicates extremely rapidly in some of the human immune cells, other cells remain unaffected. Researchers of the Paul-Ehrlich-Institut have been able to identify how monocytes protect themselves from an HIV infection.

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.

Original publications:
Berger A, Sommer AFR, Zwarg J, Hamdorf M, Welzel K, Esly N, Sylvia Panitz S, Reuter A, Ramos I, Jatiani A, Mulder LCF, Fernandez-Sesma A, Rutsch F, Simon V, König R, Flory E. SAMHD1-deficient CD14+ cells from individuals with Aicardi-Goutières syndrome are highly susceptible to HIV-1 infection. PLoS Pathog, December 8, 2012

Dr. Susanne Stöcker | idw
Further information:
http://www.pei.de
http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1002425

More articles from Life Sciences:

nachricht New way to look at cell membranes could change the way we study disease
19.11.2018 | University of Oxford

nachricht Controlling organ growth with light
19.11.2018 | European Molecular Biology Laboratory

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: UNH scientists help provide first-ever views of elusive energy explosion

Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.

Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...

Im Focus: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

Im Focus: Penn engineers develop ultrathin, ultralight 'nanocardboard'

When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure

Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Optical Coherence Tomography: German-Japanese Research Alliance hosted Medical Imaging Conference

19.11.2018 | Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

 
Latest News

New materials: Growing polymer pelts

19.11.2018 | Materials Sciences

Earthquake researchers finalists for supercomputing prize

19.11.2018 | Information Technology

Controlling organ growth with light

19.11.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>