Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

HIV protein attacks body’s innate protection system that could prevent virus’ replication

08.10.2003


Discovery could lead to development of protein-targeting drugs, OHSU researchers say



When HIV enters the human body, a fierce battle ensues between a ruthless viral protein and our long-misunderstood innate protection system. Ultimately, the protein seizes and destroys that system, and HIV replicates.

But Oregon Health & Science University researchers who discovered the mechanism by which this destruction occurs say our innate protection system could have a leg up in the mêlée if drugs can be developed to target the HIV-encoded viral protein.


"We’re thrilled about this," David Kabat, Ph.D., professor of biochemistry and molecular biology at OHSU, said of the discovery.

His OHSU collaborators were: Mariana Marin, research assistant professor, Susan Kozak, senior research associate, Department of Biochemistry and Molecular Biology; and Kristin Rose, graduate research assistant, Department of Molecular Microbiology and Immunology.

The study, published Sunday in the November issue of the journal Nature Medicine, could have major implications for AIDS research. Not only does it give scientists insights into how the body’s built-in defense system works, it’s a shot in the arm for the search for more targeted, effective anti-HIV drugs.

"This is definitely relevant to drug development and pharmacology in the fight against AIDS," Kabat said.

Kabat’s team found that the HIV-encoded protein – viral infectivity factor, or Vif – neutralizes a potent antiviral human protein called APOBEC3G that would, in the absence of Vif, inactivate HIV. Vif binds to APOBEC3G and induces its "extremely" rapid degradation, eliminating APOBEC3G from cells and keeping it from invading HIV particles where it could damage the virus’ genetic material.

APOBEC3G is a nucleic acid-editing enzyme that exists in some cells, like white blood cells, but is absent in others, such as skin cells. Cells where APOBEC3G is present are "non-permissive," meaning they don’t allow replication of an HIV mutant which lacks a Vif gene.

When HIV or another virus is detected, APOBEC3G edits and fragments the virus’ nucleic acid.

"The body has an innate system that is capable of ridding itself of HIV," Kabat said. "But Vif counteracts and neutralizes this defense system of the body, providing a safe nest in which HIV progeny get produced. Vif comes in and somehow recognizes this innate system. If Vif isn’t there, the progeny get destroyed during their birth."

Kabat’s team began work on Vif in 1997 and published its first paper on the viral protein a year later. At that time, the scientists developed insights about Vif that suggested the existence of a potent antiviral defense system in human lymphocytes, and that it was Vif’s job to destroy it.

"We knew what to look for, but we didn’t know it was APOBEC3G," Kabat said.

Scientists had known for 10 years that a relative of APOBEC3G, APOBEC1, was an nucleic acid-editing enzyme that regulates normal cellular function, but which doesn’t have an antiviral effect. Ten months ago a group of scientists in Philadelphia identified APOBEC3G as the cellular defense mechanism everyone was looking for, and the field was "cracked open."

"APOBEC3G is related to APOBEC1. That was a clue," Kabat said. "When this group in Philadelphia discovered APOBEC3G was involved in antiviral response, it was the first indication these nucleic acid-editing enzymes evolved to attack viruses."

Since making its recent discovery, the OHSU team has worked to set up a system in which Vif and APOBEC3G exist in the same cell, which will let researchers examine APOBEC3G’s destruction in more detail while allowing it to be continually produced. It also is working to develop enough Vif so its structure can be studied further.

"We’re going to try to learn exactly how Vif destroys APOBEC3G in greater and greater mechanistic detail," Kabat said.

Kabat plans to create a platform for screening potential anti-Vif drugs with the help of robotics that pull from a chemical library. The team also will work directly with drug companies on testing their products.

"The drug discovery approach is so important and we’re going to try to make a big contribution to it," he said. "The results we have provide assays, tests and information one needs to develop drugs against Vif. These tools are useful for screening drugs, but also for testing candidate drugs."

Kabat noted that the American Foundation for AIDS Research (amfAR) has put a premium on anti-Vif drug discovery. "It’s definitely been recognized as an important frontier in the fight against AIDS," he said.


The study was supported by a grant from the National Institutes of Health.

Jonathan Modie | EurekAlert!
Further information:
http://www.ohsu.edu/

More articles from Health and Medicine:

nachricht Unique brain 'fingerprint' can predict drug effectiveness
11.07.2018 | McGill University

nachricht Direct conversion of non-neuronal cells into nerve cells
03.07.2018 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Research finds new molecular structures in boron-based nanoclusters

13.07.2018 | Materials Sciences

Algae Have Land Genes

13.07.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>