About My Health Careers Internship MedBlogs Contact us
Medindia LOGIN REGISTER
Advertisement

Molecular Signals That Rouse Dormant HIV Infection Discovered

by Sheela Philomena on October 31, 2013 at 1:05 PM
Font : A-A+

 Molecular Signals That Rouse Dormant HIV Infection Discovered

Researchers have uncovered the molecular signals that guide the activation of latent HIV. Specifically, they showed how molecular crosstalk between calcium and an enzyme called calcineurin, along with a molecule called prostratin, switch on members of the NF-κB family of proteins—thereby activating latent HIV. These findings point to a new strategy of artificially activating HIV—a process that experts believe is key to flushing out all evidence of infection and developing a cure for HIV/AIDS.

During the initial stages of HIV infection, often within hours, the virus infects a type of white blood cell called CD4 T cells. In the majority of cases, HIV then hijacks the cell's DNA to produce, or "transcribe," new virus, infecting more cells. But every so often something different happens: the viral DNA inserts itself into the host cell's DNA, but then stops, maintaining a holding pattern that can persist for decades. This latent HIV is virtually undetectable and therefore cannot be targeted by medication.

Advertisement

"Current treatments, which involve a complex cocktail of antiretroviral (ARV) medications, are fine-tuned to target and destroy active, replicating HIV—but they can't touch the latent virus," explained Dr. Greene, director of virology and immunology research at Gladstone and professor of medicine at the University of California, San Francisco, with which Gladstone is affiliated. "But most troublingly is that within weeks of stopping ARV treatment, the latent virus wakes up, and the cycle of replication and infection begins all over again."

What this means for patients is a lifetime of treatment with expensive ARVs. This is an unsustainable strategy in today's world, where more than two-thirds of those infected live in the developing world and have limited access to ARVs. And for every 10 people who do receive ARVs, 16 become newly infected.
Advertisement

Recently, researchers have championed the "shock-and-kill" strategy for combating HIV latency. This approach would activate the latent virus, and then bombard this newly active virus with ARVs. Precisely how to do so has been fraught with difficulty. But in this study, Dr. Greene and his team have identified a potential strategy.

In laboratory experiments using latent HIV introduced into CD4 cells from donors or cell culture, the research team tested a series of proteins believed to regulate activation and transcription of the virus. One such family of proteins, called NFAT, was previously shown to induce HIV transcription during the initial stages of infection. So the researchers tested whether it would also function in activating latent HIV.

"Surprisingly, NFAT didn't appear to play a central role so we went back to the drawing board, exploring other protein families we thought might be involved," said Gladstone Postdoctoral Fellow Jonathan Chan, PhD, the paper's lead author. "Interestingly, we observed that members of the NF-κB protein family appeared to act as a molecular alarm clock, rousing latent HIV and spurring viral replication."

Even more interesting was what they observed when they added prostratin to the mix. Prostratin, a naturally occurring compound that is extracted from the Samoan mamala tree, helps to activate latent HIV. But prostratin is difficult to procure and, as of right now, impossible to synthesize on an industrial scale. Now, the experiments performed by Drs. Greene and Chan suggest a potential workaround.

"When we stimulated the calcium/calcineurin pathway in the presence of low levels of prostratin, we in turn boosted prostratin's effectiveness," explained Dr. Chan. "These findings, while preliminary, hold promise that we could develop a way to purge the latent HIV reservoir with even suboptimal levels of prostratin."

"Our results give us much-needed insight how the shock-and-kill approach to eliminate the virus might work," said Dr. Greene. "Slowly but surely we are finding new components of a cure cocktail that might be able—at long last—to realize a broadly applicable and scaleable cure for HIV/AIDS."

Source: Eurekalert
Advertisement

Advertisement
News A-Z
A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
News Category
What's New on Medindia
Health Benefits of Sea Buckthorn
Contraceptive Pills in Polycystic Ovary Syndrome (PCOS) Curtail Type 2 Diabetes Risk
Mushroom May Help Cut Down the Odds of Developing Depression
View all

Medindia Newsletters Subscribe to our Free Newsletters!
Terms & Conditions and Privacy Policy.

More News on:
Oral Health And AIDS AIDS/HIV AIDS/HIV - Epidemiology AIDS/HIV - Clinical Features AIDS/HIV - Health Education AIDS/HIV - Prevention And Transmission AIDS / HIV - Treatment AIDS/HIV- Lab Tests and Faqs Prostitution: Fresh Stakes in the Oldest Trade Flu 

Recommended Reading
AIDS/HIV - Prevention And Transmission
Encyclopedia section of medindia explains in brief about the prevention for AIDS/HIV...
Quiz on HIV Symptoms
Do you know that there are symptoms for each stage of HIV/AIDS? Learn more from our HIV Symptom ......
Older Children With HIV may Need to Start Treatment Sooner
Younger children with HIV are at high risk of disease progression if not treated on time....
AIDS / HIV - Treatment
Encyclopedia section of medindia explains in brief about the treatment for AIDS/HIV...
AIDS/HIV
"AIDS is an epidemic disease, a potentially preventable, deadly infection for which there is no cure...
AIDS/HIV - Clinical Features
Encyclopedia section of medindia gives general info about HIV Clinical Features...
AIDS/HIV - Epidemiology
AIDS or HIV is an epidemic disease, a potentially deadly infection that can be prevented with preca...
AIDS/HIV - Health Education
Encyclopedia section of medindia gives general info about AIDS information and health education....
Oral Health And AIDS
AIDS has taken on massive proportions in modern times. It is estimated that over 15 million people a...
Prostitution: Fresh Stakes in the Oldest Trade
Prostitution has broadened its base to include street prostitution, massage brothels, gigolo outcall...

Disclaimer - All information and content on this site are for information and educational purposes only. The information should not be used for either diagnosis or treatment or both for any health related problem or disease. Always seek the advice of a qualified physician for medical diagnosis and treatment. Full Disclaimer

© All Rights Reserved 1997 - 2021

This site uses cookies to deliver our services. By using our site, you acknowledge that you have read and understand our Cookie Policy, Privacy Policy, and our Terms of Use