Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study holds promise for new way to fight HIV

05.09.2005


Novel approach may address viral resistance

Researchers have confirmed for the first time the benefit of an innate defense system present in the few patients who remain healthy after years of infection with HIV despite receiving no treatment, according to an article published in the September edition of the Journal of Virology. The study found that the subset of HIV-infected patients referred to as long-term survivors or nonprogressors have higher amounts of a key enzyme in their white blood cells. At the same time, a related biotech company is poised to begin preclinical testing on a drug designed to confer similar protection on most HIV patients.

Approximately five percent of patients with HIV, or human immunodeficiency virus, do not develop AIDS, or do so very slowly. Researchers have been trying for years to understand what sets long-term nonprogressors apart. Past research suggested that such patients maintain higher levels of an enzyme in white blood cells called APOBEC-3G (A3G), and the new study confirmed it in the first experiments on human cells.



Researchers at the University of Rochester Medical Center believe that A3G "edits," or introduces changes in, the HIV genetic code every time the virus copies itself. By doing so, A3G corrupts the HIV gene code and prevents the virus from reproducing. Unfortunately, HIV has evolved to counter A3G with viral infectivity factor (Vif), a protein that "grabs" A3G and tricks the body into destroying it. With the "editing enzyme" gone, HIV is free to overwhelm the immune system, leaving patients vulnerable to AIDS infections that take three million lives per year.

"Unlike nonprogressors, we believe that most people do not make enough A3G to overcome the efforts by Vif to shut it down," said Harold C. Smith, Ph.D., professor of Biochemistry and Biophysics at the University of Rochester Medical Center, co-author of the J. Virology paper and a founder of the biotech company, OyaGen Inc. "Our work supports Michael Malim’s seminal discovery while at the University of Pennsylvania, which suggested that protecting whatever amount of A3G that people do have from Vif represents a new way to attack HIV."

Study Details

For two decades, medical center researchers have worked to determine how families of editing enzymes, including A3G, make changes to DNA and RNA. The immune system recognizes the ability of editing enzymes to cause rapid genetic change and unleashes them on viral DNA. Researchers believe that the enzymes change the HIV genetic code so extensively that the virus loses the ability to code for its own proteins and can no longer reproduce.

To confirm that A3G offers strong protection against HIV, researchers in the current study measured A3G levels in the immune cells of six people not infected with HIV and in 25 patients with the virus. Of those with HIV, eight were long-term nonprogressors and seventeen had normal disease progression. None of those studied were receiving antiretroviral therapy at the time blood was drawn.

In the study, the researchers found that higher levels of A3G closely corresponded to lower HIV viral levels. In addition, higher levels of A3G were closely associated with higher CD4 T cell counts. Unless destroyed by HIV, helper T cells with CD-4 receptors target bodily invaders for full-scale attack by the immune system. Furthermore, the team determined that nonprogressors have the most A3G editing enzyme, followed by those not infected with HIV and lastly by those progressing toward full-blown AIDS.

"Our study is immediately relevant to HIV research in several important areas," said Xia Jin, M.D., Ph.D., assistant professor of Medicine at the medical center and lead author of the J. Virology paper. "In diagnostics, the work will establish a new prognostic marker for AIDS by enabling the measurement of A3G levels in HIV-infected patients. It will also clarify a previously unrecognized mechanism that underlies slower disease progression in long-term nonprogressors. Lastly, the data suggest that protecting A3G from viral attack may be an important new way to treat AIDS and other viral infections," Jin said. A New Approach to HIV Treatment

Smith, with support from the University of Rochester Technology Seed Fund, formed OyaGen in 2003. The biotech startup seeks to exploit a family of 14 editing enzymes and related proteins as novel targets for the development of pharmaceuticals.

While OyaGen’s platform technology has the potential to address several disease areas, the first focus is the treatment of HIV. The company’s lead drug candidate interferes with ability of Vif to disable A3G. The experimental treatment is based on the work of Hui Zhang, M.D., Ph.D., associate professor of Medicine at Thomas Jefferson University (TJU) and on technology licensed from TJU.

As a dimer, Vif is able to come together like the two arms in a pair of pliers to "grab" A3G. Once attached to A3G, Vif flags it for destruction as part of an otherwise healthy protein recycling process. OyaGen’s drug, a Vif Dimerization Antagonist (VDA), prevents the two halves of Vif from linking up and leaves A3G free to "catastrophically mutate" the HIV genetic code. In early experiments, OyaGen’s therapeutic has been successful in reducing HIV infectivity.

OyaGen recently completed an initial $1.5 million fundraising round with investors including the technology seed fund and private individuals. The resources will support research and pave the way for safety, toxicology, bioavailability and mode of delivery studies to begin in October. Based on early successes, the company now seeks to raise between $10 million and $30 million to fund pre-clinical trials and to support negotiations with the U.S. Food and Drug Administration on the submission of a new drug application planned for 2006.

In addition, OyaGen in July signed a licensing agreement with the University of Rochester for rights to the technology developed by Smith. The agreement covers novel drug targets with the aim of protecting A3G from viral attack. It also establishes a laboratory in the university’s technology incubator space.

"We hope to develop the first drug that solves the problem of viral resistance, where viral strains have changed so quickly that HIV is resistant to current treatments in 40 percent of new cases," Smith said. "Our theory is that if the virus attempts to outsmart our drug by changing Vif, it will leave itself open to attack by A3G. If early studies go as planned, OyaGen may be able to offer a treatment that HIV cannot easily escape."

Greg Williams | EurekAlert!
Further information:
http://www.urmc.rochester.edu/

More articles from Studies and Analyses:

nachricht Study relating to materials testing Detecting damages in non-magnetic steel through magnetism
23.07.2018 | Technische Universität Kaiserslautern

nachricht Innovative genetic tests for children with developmental disorders and epilepsy
11.07.2018 | Christian-Albrechts-Universität zu Kiel

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: It’s All in the Mix: Jülich Researchers are Developing Fast-Charging Solid-State Batteries

There are currently great hopes for solid-state batteries. They contain no liquid parts that could leak or catch fire. For this reason, they do not require cooling and are considered to be much safer, more reliable, and longer lasting than traditional lithium-ion batteries. Jülich scientists have now introduced a new concept that allows currents up to ten times greater during charging and discharging than previously described in the literature. The improvement was achieved by a “clever” choice of materials with a focus on consistently good compatibility. All components were made from phosphate compounds, which are well matched both chemically and mechanically.

The low current is considered one of the biggest hurdles in the development of solid-state batteries. It is the reason why the batteries take a relatively long...

Im Focus: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

Biosensor allows real-time oxygen monitoring for 'organs-on-a-chip'

21.08.2018 | Medical Engineering

Researchers discover link between magnetic field strength and temperature

21.08.2018 | Physics and Astronomy

IHP technology ready for space flights

21.08.2018 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>