Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists discover enzyme crucial to HIV replication

01.11.2004


Scientists have discovered that a cellular enzyme helps ferry HIV genetic instructions out of the cell nucleus where they can then be translated into proteins to begin their most destructive work. The cellular enzyme represents a potential new target for developing improved HIV drugs, say the researchers from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and the McGill University AIDS Center.



Kuan-Teh Jeang, M.D., Ph.D., of NIAID led the research team reporting their discovery in the Oct. 29 issue of Cell. "This finding provides new insights into a crucial step in HIV replication," says Anthony S. Fauci, M.D., director of NIAID. "The discovery also provides an attractive target for drug development which, if successful, might in time give us a completely new type of HIV drug that circumvents the problem of drug resistance."

Dr. Jeang’s team found evidence that the virus co-opts an enzyme produced by human cells to transport HIV’s genetic material out of the cell nucleus. Once out of the nucleus, these messenger RNAs begin directing the cell to create and assemble new virus particles.


The process of how HIV genetic material--a long unedited strand of RNA--exits the cell nucleus has long puzzled scientists. Human cells cut, edit and splice RNA before it can leave the nucleus, but somehow HIV subverts that process and exports from the nucleus the long version of RNA that encodes instructions for making new viral particles.

Scientists knew that HIV makes a protein called Rev to help skirt the prohibition on transporting the lengthy, unedited version of RNA from the nucleus. They also knew that HIV commandeers a human protein known as CRM1 to aid in this process. Rev and CRM1 together, however, are insufficient to explain how HIV flouts the molecular machinery that cuts and splices RNA before it leaves the nucleus.

"Unspliced RNA is like an unwieldy ball of yarn," explains Dr. Jeang. "We found that the virus also uses a human enzyme known as DDX3 to straighten its RNA before threading it through a small pore in the nucleus." The team’s experiments offer the first evidence that HIV uses DDX3 in the complex process that moves its RNA out of the nucleus. They also demonstrated that DDX3, a human RNA helicase enzyme, is essential to this process. RNA helicases are enzymes that untwist RNA molecules.

The researchers now plan to look for inhibitors, small molecules that could either lock or gum up DDX3’s ability to straighten a twisted strand of RNA. Although it would take many years to develop, in the best scenario, an inhibitor for DDX3 could effectively block HIV replication. Researchers would need to find a balance between a potential inhibitor’s action in shutting down viral replication and any detriment it might cause to human cells.

In the past decade, two classes of HIV inhibitor drugs, protease inhibitors and reverse transcriptase inhibitors, have greatly extended the lives of HIV-positive individuals. While these drugs target HIV enzymes, a DDX3 inhibitor would target a cellular enzyme. The researchers see a great therapeutic advantage to blocking a cellular enzyme rather than a viral enzyme.

"Unlike viral enzymes, cellular enzymes can not mutate to escape from drugs," says Dr. Jeang. The problem of drug resistance that occurs with protease and reverse transcriptase inhibitors might thus be eliminated with a successful DDX3 inhibitor.

Linda Joy | EurekAlert!
Further information:
http://www.niaid.nih.gov

More articles from Life Sciences:

nachricht Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Water - as the underlying driver of the Earth’s carbon cycle

17.01.2017 | Earth Sciences

Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

17.01.2017 | Materials Sciences

Smart homes will “LISTEN” to your voice

17.01.2017 | Architecture and Construction

VideoLinks
B2B-VideoLinks
More VideoLinks >>>