'Shock and kill' research gives new hope for HIV-1 eradication

Jun 04, 2009

Latent HIV genes can be 'smoked out' of human cells. The so-called 'shock and kill' technique, described in a preclinical study in BioMed Central's open access journal Retrovirology, might represent a new milestone along the way to the discovery of a cure for HIV/AIDS.

Dr. Enrico Garaci, president of the Istituto Superiore di Sanità (the Italian Institute of Health) and Dr. Andrea Savarino, a retrovirologist working at the institution, worked with a team of researchers to study the so-called "barrier of latency" which has been the main obstacle to HIV eradication from the body.

Cells harbouring a quiescent HIV genome are responsible for HIV persistence during therapy. In other words, HIV-1 genes become pieces of the human organism, and many scientists have simply thought there is nothing we can do. Dr Savarino's team aimed to 'smoke out' the virus in order to render the latently infected cells targetable by the immune system or artificial means. They write, "This can be achieved using inhibitors of histone deacetylases (HDACs), which are a class of enzymes that maintain HIV latency. However, their effects on HIV are evident only when used in toxic quantities".

To overcome this problem, the Italian researchers tested a collection of HDAC inhibitors, some of which specifically target only certain enzyme isoforms (class I HDACs) that are involved in HIV latency. The toxicity of this approach, however, was not markedly decreased, although it compromises a more limited number of cellular pathways. Moreover, at non-toxic quantities, class I HDAC inhibitors were able to induce the 'awakening' of a portion of cells within a latently infected cell population. The researchers then repeated the experiment adding a drug inducing oxidative stress, buthionine sulfoximine (BSO). The results showed that BSO recruited cells non-responsive to the HDAC inhibitors into the responding . An important result was that the infected cells' 'awakening' was followed by cell death, whereas the non-infected cells were left intact by the drug combination.

"I really hope this study may open new avenues to the development of weapons able to eliminate the HIV-infected cells from the body", says Dr. Andrea Savarino, "Such weapons, in combination with antiretroviral therapies, could hopefully allow people living with HIV/AIDS to get rid of the virus and return to a normal life. Of note, there are testable drug combinations composed of molecules that have passed phase I clinical trials for safety in humans". This type of approach has been dubbed 'shock and kill'. "Although this type of approach is largely accepted by the scientific community", adds Dr. Savarino, "to be honest, we have to take into consideration that some scientists are skeptical about this approach, and others even think that a cure for /AIDS will never be found. Experiments using animal models will shed a new light on this difficult problem."

More information: "Shock and kill" effects of class I-selective histone deacetylase inhibitors in combination with the glutathione synthesis inhibitor buthionine sulfoximine in cell line models for HIV-1 quiescence; Andrea Savarino, Antonello Mai, Sandro Norelli, Sary El Daker, Sergio Valente, Dante Rotili, Lucia Altucci, Anna Teresa Palamara and Enrico Garaci; Retrovirology 2009, 6:52 doi:10.1186/1742-4690-6-52
Article available at journal website: www.retrovirology.com/content/6/1/52

Source: BioMed Central (news : web)

Explore further: Cell-associated HIV mucosal transmission: The neglected pathway

add to favorites email to friend print save as pdf

Related Stories

Can periodontal disease act as a risk factor for HIV-1?

Apr 03, 2009

Today, during the 87th General Session of the International Association for Dental Research, convening at the Miami Beach Convention Center, a group of scientists from Nihon University (Tokyo, Japan) will present findings ...

Waking up dormant HIV

Mar 16, 2009

HAART (highly active anti-retroviral therapy) has emerged as an extremely effective HIV treatment that keeps virus levels almost undetectable; however, HAART can never truly eradicate the virus as some HIV always remains ...

How HIV hides itself

Apr 01, 2008

Researchers have discovered how Human Immunodeficiency Virus (HIV), which causes AIDS, can hide itself in our cells and dodge the attention of our normal defences, scientists heard today at the Society for General Microbiology’s ...

Neural progenitor cells as reservoirs for HIV in the brain

Mar 04, 2008

Impaired brain function is a prominent and still unsolved problem in AIDS . Shortly after an individual becomes infected with HIV, the virus can invade the brain and persist in this organ for life. Many HIV-infected individuals ...

Recommended for you

Cambodia orders probe into mass HIV infection

Dec 18, 2014

Cambodian Prime Minister Hun Sen on Thursday ordered a probe into an apparent mass HIV infection believed to have been spread by contaminated needles, as the number of suspected cases passed 100.

A fresh setback for efforts to cure HIV infection

Dec 17, 2014

Researchers are reporting another disappointment for efforts to cure infection with the AIDS virus. Six patients given blood-cell transplants similar to one that cured a man known as "the Berlin patient" have ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.