PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Gladstone scientists identify molecular signals that rouse dormant HIV infection

Activating dormant virus key to purging viral infection and developing a cure for HIV/AIDS

2013-10-31
(Press-News.org) Contact information: Anne Holden
anne.holden@gladstone.ucsf.edu
415-734-2534

Gladstone scientists identify molecular signals that rouse dormant HIV infection Activating dormant virus key to purging viral infection and developing a cure for HIV/AIDS

SAN FRANCISCO, CA—October 30, 2013—Perhaps the single greatest barrier to curbing the spread of HIV/AIDS is the dormant, or "latent," reservoir of virus, which is out of reach of even the most potent medications. But now, scientists at the Gladstone Institutes have uncovered new clues that may help researchers awaken HIV from its slumber—laying the foundation for purging all trace of the virus, and for one day finding a cure for the more than 34 million people worldwide living with HIV/AIDS.

In a paper being published today in PLOS One, researchers in the laboratory of Gladstone Investigator Warner C. Greene, MD, PhD, 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.

"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.

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."



INFORMATION:



Darshanna Bhattacharyya, Kara Lassen and Debbie Ruelas also participated in this research at Gladstone, which was funded by the National Institute of Health grant #U19 AI096113.

About the Gladstone Institutes

Gladstone is an independent and nonprofit biomedical-research organization dedicated to accelerating the pace of scientific discovery and innovation to prevent, treat and cure cardiovascular, viral and neurological diseases. Gladstone is affiliated with the University of California, San Francisco.



ELSE PRESS RELEASES FROM THIS DATE:

Is medical education in a bubble market?

2013-10-31
Is medical education in a bubble market? Lowering the cost of health care requires lowering the cost of medical education PHILADELPHIA – The costs of medical education must be reduced as part of efforts to reign in health care ...

New experiments reveal the types of bacteria involved in human decomposition

2013-10-31
New experiments reveal the types of bacteria involved in human decomposition A new field of forensic science turns its attention to bacteria The type of bacteria involved in human decomposition can change over time, according to new research published October 30th ...

Listening to music before you're even born may boost your auditory system

2013-10-31
Listening to music before you're even born may boost your auditory system Prenatal music exposure leads to long-lasting changes in the brain after birth Playing music while you're pregnant may influence your child's auditory system, according to new research published ...

One of the oldest cases of tuberculosis is discovered

2013-10-31
One of the oldest cases of tuberculosis is discovered Scientists verify the presence of tuberculosis from 7,000 years ago Tuberculosis was present in Europe as early as 7000 years ago, according to new research published October 30th in the open-access journal PLOS ...

Baby brains are tuned to the specific actions of others

2013-10-31
Baby brains are tuned to the specific actions of others Observing body movements activates related brain regions in infants Infant brains are surprisingly sensitive to other people's movements, according to new research published October 30th in the open-access journal ...

First results from LUX dark matter detector rule out some candidates

2013-10-31
First results from LUX dark matter detector rule out some candidates Results from the first run of the Large Underground Xenon (LUX) experiment operating a mile underground in the Black Hills of South Dakota, have proven the detector's sensitivity and ruled ...

Babies can learn their first lullabies in the womb

2013-10-31
Babies can learn their first lullabies in the womb The study focused on 24 women during the final trimester of their pregnancies. Half of the women played the melody of Twinkle Twinkle Little Star to their fetuses five days a week for the final stages ...

New SARS-like coronavirus discovered in Chinese horseshoe bats

2013-10-31
New SARS-like coronavirus discovered in Chinese horseshoe bats 10 years after SARS outbreak -- Ecohealth Alliance finds plausible evidence for direct bat to human transmission NEW YORK – October 30, 2013 – EcoHealth Alliance, a nonprofit organization that ...

Mystery planet baffles astronomers

2013-10-31
Mystery planet baffles astronomers Kepler-78b is a planet that shouldn't exist. This scorching lava world circles its star every eight and a half hours at a distance of less than one million miles - one of the tightest known orbits. ...

New multiple action intestinal hormone corrects diabetes

2013-10-31
New multiple action intestinal hormone corrects diabetes Scientists from the Helmholtz Zentrum Muenchen and the Technische Universitaet Muenchen, together with scientists in the USA, have ...

LAST 30 PRESS RELEASES:

Being physically active, even just a couple of days a week, may be key to better health

High-fat diet promote breast cancer metastasis in animal models

A router for photons

Nurses and AI collaborate to save lives, reduce hospital stays

Multi-resistance in bacteria predicted by AI model

Tinker Tots: A citizen science project to explore ethical dilemmas in embryo selection

Sensing sickness

Cost to build multifamily housing in California more than twice as high as in Texas

Program takes aim at drinking, unsafe sex, and sexual assault on college campuses

Inability to pay for healthcare reaches record high in U.S.

Science ‘storytelling’ urgently needed amid climate and biodiversity crisis

KAIST Develops Retinal Therapy to Restore Lost Vision​

Adipocyte-hepatocyte signaling mechanism uncovered in endoplasmic reticulum stress response

Mammals were adapting from life in the trees to living on the ground before dinosaur-killing asteroid

Low LDL cholesterol levels linked to reduced risk of dementia

Thickening of the eye’s retina associated with greater risk and severity of postoperative delirium in older patients

Almost one in ten people surveyed report having been harmed by the NHS in the last three years

Enhancing light control with complex frequency excitations

New research finds novel drug target for acute myeloid leukemia, bringing hope for cancer patients

New insight into factors associated with a common disease among dogs and humans

Illuminating single atoms for sustainable propylene production

New study finds Rocky Mountain snow contamination

Study examines lactation in critically ill patients

UVA Engineering Dean Jennifer West earns AIMBE’s 2025 Pierre Galletti Award

Doubling down on metasurfaces

New Cedars-Sinai study shows how specialized diet can improve gut disorders

Making moves and hitting the breaks: Owl journeys surprise researchers in western Montana

PKU Scientists simulate the origin and evolution of the North Atlantic Oscillation

ICRAFT breakthrough: Unlocking A20’s dual role in cancer immunotherapy

How VR technology is changing the game for Alzheimer’s disease

[Press-News.org] Gladstone scientists identify molecular signals that rouse dormant HIV infection
Activating dormant virus key to purging viral infection and developing a cure for HIV/AIDS