Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

HIV virulence depends on where virus inserts itself in host DNA

13.11.2014

Retargeting integration site to ‘safer’ part of host DNA may lead to new therapies

The human immunodeficiency virus (HIV) can insert itself at different locations in the DNA of its human host – and this specific integration site determines how quickly the disease progresses, report researchers at KU Leuven’s Laboratory for Molecular Virology and Gene Therapy. Their study was published online today in the journal Cell Host & Microbe.


The HIV protein integrase (blue) can insert viral DNA (red) at different locations in the DNA of its human host (orange). But how the virus selects its insertion points has puzzled virologists for over 20 years.

When HIV enters the bloodstream, virus particles bind to and invade human immune cells. HIV then reprogrammes the hijacked cell to make new HIV particles.

The HIV protein integrase plays a key role in this process: it recognises a short segment in the DNA of its host and catalyzes the process by which viral DNA is inserted in host DNA.

Integrase can insert viral DNA at various places in human DNA. But how the virus selects its insertion points has puzzled virologists for over 20 years.

Now a team of KU Leuven researchers has discovered that the answer lies in two amino acids. Doctoral researcher Jonas Demeulemeester, first author of the study, explains: “HIV integrase is made up of a chain of more than 200 amino acids folded into a structure. By modelling this structure, we found two positions in the protein that make direct contact with the DNA of the host. These two amino acids determine the integration site. This is not only the case for HIV but also for related animal-borne viruses.”

Viral variants

In a second phase of the study, the researchers were able to manipulate the integration site choice of HIV, explains Professor Rik Gijsbers. “We changed the specific HIV integrase amino acids for those of animal-borne viruses and found that the viral DNA integrated in the host DNA at locations where the animal-borne virus normally would have done so.”

“We also showed that HIV integrases can vary,” says Professor Rik Gijsbers. “Sometimes different amino acids appeared in the two positions we identified. These variant viruses also integrate into the host DNA at a different site than the normal virus does.”

Together with Dr. Thumbi Ndung’u (University of KwaZulu-Natal, Durban, South Africa), the team studied the impact of these viral variants on the progression towards AIDS in a cohort of African HIV patients, continues Professor Zeger Debyser: “To our surprise, we found that the disease progressed more quickly when the integration site was changed. In other words, the variant viruses broke down the immune system more rapidly. This insight both increases our knowledge of the disease and opens new perspectives. By retargeting the integration site to a ‘safer’ part of the host DNA, we hope to eventually develop new therapies.”

Jonas Demeulemeester | EurekAlert!
Further information:
http://www.kuleuven.be/english/news/hiv-virulence-depends-on-where-virus-inserts-itself-in-host-dna

More articles from Life Sciences:

nachricht Individual Receptors Caught at Work
19.10.2017 | Julius-Maximilians-Universität Würzburg

nachricht Rapid environmental change makes species more vulnerable to extinction
19.10.2017 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

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...

Im Focus: Breaking: the first light from two neutron stars merging

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....

Im Focus: Smart sensors for efficient processes

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...

Im Focus: Cold molecules on collision course

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...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Rapid environmental change makes species more vulnerable to extinction

19.10.2017 | Life Sciences

Integrated lab-on-a-chip uses smartphone to quickly detect multiple pathogens

19.10.2017 | Interdisciplinary Research

Fossil coral reefs show sea level rose in bursts during last warming

19.10.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>