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 New malaria analysis method reveals disease severity in minutes
14.08.2017 | University of British Columbia

nachricht New type of blood cells work as indicators of autoimmunity
14.08.2017 | Instituto de Medicina Molecular

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: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>