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 Polymers Based on Boron?
18.01.2018 | Julius-Maximilians-Universität Würzburg

nachricht Bioengineered soft microfibers improve T-cell production
18.01.2018 | Columbia University School of Engineering and Applied Science

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

Im Focus: A thermometer for the oceans

Measurement of noble gases in Antarctic ice cores

The oceans are the largest global heat reservoir. As a result of man-made global warming, the temperature in the global climate system increases; around 90% of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Polymers Based on Boron?

18.01.2018 | Life Sciences

Bioengineered soft microfibers improve T-cell production

18.01.2018 | Life Sciences

World’s oldest known oxygen oasis discovered

18.01.2018 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>