Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Jefferson Scientists Uncover HIV Escape Route from Drugs and Vaccines

30.05.2003


Virologists at Jefferson Medical College may have discovered a new way by which HIV, the AIDS virus, can evade both anti-viral drugs and vaccines.



Researchers had reported last summer that a protein called CEM15 is a natural inhibitor of HIV, acting as a brake on HIV’s replication. They also showed that an HIV-encoded protein, Vif, or Virion infectivity factor, counteracts CEM15. Vif, in effect, is a shield to protect HIV from a host cell’s defenses.

But how CEM15 worked was something of a mystery. Now, Hui Zhang, M.D., Ph.D., Bin Yang, Ph.D., and their colleagues at Jefferson Medical College of Thomas Jefferson University in Philadelphia have found that CEM15 renders HIV essentially dead by altering newly made HIV DNA, causing mutations and preventing replication.


At the same time, the researchers showed that HIV and Vif can subvert this system, enabling the virus to instead make myriad mutations of itself. The major obstacle to creating anti-HIV drugs and vaccines is the virus’ propensity to mutate quickly and often. The researchers report their findings this week in an advanced online publication in the journal Nature.

“This is an important finding because it may be a reason why HIV can escape from vaccines and develop resistance to antiviral drugs,” says virologist Roger J. Pomerantz, M.D., professor of medicine, biochemistry and molecular pharmacology and director of the Center for Human Virology and Biodefense at Jefferson Medical College and a co-author on the Nature paper.

According to Dr. Zhang, who is an associate professor of medicine at Jefferson Medical College, Vif is a regulatory protein needed for the virus to grow and make infectious viruses from certain cells. CEM15 is relative newcomer to the known array of host defense systems.

But little was known about how CEM15 inhibited viral replication. In the Nature paper, he and his colleagues describe results from work in their laboratory showing that CEM15 attacks newly synthesized viral DNA. CEM15 works by either biochemically degrading such DNA or alternatively, causing a “lethal hypermutation,” killing the virus.

In the process of replicating, HIV mutates at a rate 1,000 times higher than normal cells. This high rate of mutation during replication, Dr. Zhang says, has been thought to be the driving force behind viral genetic variation – and the reason it has been so difficult to create treatments against – or prevent – HIV infection.

“No one knew the entire reason why HIV makes a hypermutation,” he says, explaining that during a process called reverse transcription (RT) that occurs in replication, the HIV mutation rate greatly increases. “This paper shows that hypermutations aren’t only caused by HIV RT, but are also made by CEM15, a host defense system.

“HIV is smart,” he says. “The virus sees CEM15 is going to use hypermutation as a way to defeat and kill it. The virus uses a shield, Vif, to protect itself. At the same time, the virus hijacks the antiviral defense system and uses a ‘non-lethal’ hypermutation process to make more mutations. It turns it into its own weapon.”

Accumulating such non-lethal hypermutations means HIV is essentially “using CEM15 to drive genetic variation,” Dr. Zhang says. “These are preliminary data, but it is a beginning,” he says. “It is not an answer, but opens the door for more research. People have to think about the fact that host defense-caused hypermutation may play a role in genetic variation. It could be a key to know how HIV resists drugs and escapes from immunosurveillance and vaccines. The researchers are now working on trying to better understand how HIV Vif fights back against CEM15.

Steven Benowitz | TJUH
Further information:
http://www.jeffersonhospital.org/news/e3front.dll?durki=16476

More articles from Health and Medicine:

nachricht The end of pneumonia? New vaccine offers hope
23.10.2017 | University at Buffalo

nachricht Scientists track ovarian cancers to site of origin: Fallopian tubes
23.10.2017 | Johns Hopkins Medicine

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: Salmonella as a tumour medication

HZI researchers developed a bacterial strain that can be used in cancer therapy

Salmonellae are dangerous pathogens that enter the body via contaminated food and can cause severe infections. But these bacteria are also known to target...

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

3rd Symposium on Driving Simulation

23.10.2017 | Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

 
Latest News

Microfluidics probe 'cholesterol' of the oil industry

23.10.2017 | Life Sciences

Gamma rays will reach beyond the limits of light

23.10.2017 | Physics and Astronomy

The end of pneumonia? New vaccine offers hope

23.10.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>