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 Nonstop Tranport of Cargo in Nanomachines
20.11.2018 | Max-Planck-Institut für molekulare Zellbiologie und Genetik

nachricht Researchers find social cultures in chimpanzees
20.11.2018 | Universität Leipzig

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Nonstop Tranport of Cargo in Nanomachines

Max Planck researchers revel the nano-structure of molecular trains and the reason for smooth transport in cellular antennas.

Moving around, sensing the extracellular environment, and signaling to other cells are important for a cell to function properly. Responsible for those tasks...

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.

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

Nonstop Tranport of Cargo in Nanomachines

20.11.2018 | Life Sciences

Researchers find social cultures in chimpanzees

20.11.2018 | Life Sciences

When AI and optoelectronics meet: Researchers take control of light properties

20.11.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>