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:

Einstein Probe releases its Science White Paper

Music-based therapy may improve depressive symptoms in people with dementia

No evidence that substituting NHS doctors with physician associates is necessarily safe

At-home brain speed tests bridge cognitive data gaps

CRF appoints Josep Rodés-Cabau, M.D., Ph.D., as editor-in-chief of structural heart: the journal of the heart team

Violent crime is indeed a root cause of migration, according to new study

Customized smartphone app shows promise in preventing further cognitive decline among older adults diagnosed with mild impairment

Impact of COVID-19 on education not going away, UM study finds

School of Public Health researchers receive National Academies grant to assess environmental conditions in two Houston neighborhoods

Three Speculum articles recognized with prizes

ACM A.M. Turing Award honors two researchers who led the development of cornerstone AI technology

Incarcerated people are disproportionately impacted by climate change, CU doctors say

ESA 2025 Graduate Student Policy Award Cohort Named

Insomnia, lack of sleep linked to high blood pressure in teens

Heart & stroke risks vary among Asian American, Native Hawaiian & Pacific Islander adults

Levels of select vitamins & minerals in pregnancy may be linked to lower midlife BP risk

Large study of dietary habits suggests more plant oils, less butter could lead to better health

Butter and plant-based oils intake and mortality

20% of butterflies in the U.S. have disappeared since 2000

Bacterial ‘jumping genes’ can target and control chromosome ends

Scientists identify genes that make humans and Labradors more likely to become obese

Early-life gut microbes may protect against diabetes, research in mice suggests

Study raises the possibility of a country without butterflies

Study reveals obesity gene in dogs that is relevant to human obesity studies

A rapid decline in US butterfly populations

Indigenous farming practices have shaped manioc’s genetic diversity for millennia

Controlling electrons in molecules at ultrafast timescales

Tropical forests in the Americas are struggling to keep pace with climate change

Brain mapping unlocks key Alzheimer’s insights

Clinical trial tests novel stem-cell treatment for Parkinson’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