Enlisting the AIDS virus to fight cancer

August 29, 2012
Infographic representation of the HIV contamination process. © CNRS Photothèque/www.gregcirade.com

(Medical Xpress)—Can HIV be transformed into a biotechnological tool for improving human health? According to a CNRS team at the Architecture et Réactivité de l'ARN (RNA Architecture and Reactivity) laboratory, the answer is yes. Taking advantage of the HIV replication machinery, the researchers have been able to select a specific mutant protein. Added to a culture of tumor cells in combination with an anticancer drug, this protein improves the effectiveness of the treatment at 1/300 the normal dosage levels. Published in PLoS Genetics on 23 August 2012, these findings could lead to long-term therapeutic applications in the treatment of cancer and other pathologies.

The (HIV), which causes AIDS, uses human cell material to multiply, primarily by inserting its genetic material into the host cells' genome (see illustration below). The distinctive characteristic of HIV is that it mutates constantly, and consequently generates several mutant proteins (or variants) in the course of its successive multiplications. This phenomenon allows the virus to adapt to repeated environmental changes and resist the antiviral treatments that have been developed so far.

At the IBMC (Institut de Biologie Moléculaire et Cellulaire) in Strasbourg, the researchers of the CNRS Architecture et Réactivité de l'ARN laboratory had the idea of using this multiplication strategy to rechannel the effects of the virus for therapeutic purposes, in particular the treatment of cancer.

They first altered the by introducing a human gene that is found in all cells: the gene for deoxycytidine kinase (dCK), a protein that activates anticancer drugs.  Researchers have been trying to produce a more effective form of dCK for several years. Through HIV multiplication, the CNRS team has selected a "library" of nearly 80 mutant proteins and tested them on tumor cells in the presence of an anticancer drug. The results have enabled them to identify a dCK variant that is more effective than the wild-type (non-mutated) protein, inducing the death of tumor cells in culture. In combination with this protein, the anticancer drugs showed identical effectiveness at 1/300 the dose. The possibility of reducing the doses of anticancer drugs would palliate the problems posed by their components' toxicity, reduce their side effects and, most importantly, improve their effectiveness.

One advantage of this experimental technique is that the mutant proteins were tested directly on cells in culture. The next step in the years to come will be preclinical (animal) studies on the isolated . In addition, this experimental system using a normally life-threatening virus is likely to lead to a great many other therapeutic applications.

Explore further: Drug designer: New tool reveals mutations that cause HIV-drug resistance

More information: Retrovolution: HIV-driven Evolution of Cellular Genes and Improvement of Anticancer Drug Activation, Rossolillo P., Winter F., Simon-Loriere E., Gallois-Montbrun S. and Negroni M. PLoS Genetics, 23 August 2012.

Related Stories

Drug designer: New tool reveals mutations that cause HIV-drug resistance

July 8, 2011
Protease inhibitor drugs are one of the major weapons in the fight against HIV, the virus that causes AIDS, but their effectiveness is limited as the virus mutates and develops resistance to the drugs over time. Now a new ...

Recommended for you

Scientists provide insight into genetic basis of neuropsychiatric disorders

July 21, 2017
A study by scientists at the Children's Medical Center Research Institute at UT Southwestern (CRI) is providing insight into the genetic basis of neuropsychiatric disorders. In this research, the first mouse model of a mutation ...

Scientists identify new way cells turn off genes

July 19, 2017
Cells have more than one trick up their sleeve for controlling certain genes that regulate fetal growth and development.

South Asian genomes could be boon for disease research, scientists say

July 18, 2017
The Indian subcontinent's massive population is nearing 1.5 billion according to recent accounts. But that population is far from monolithic; it's made up of nearly 5,000 well-defined sub-groups, making the region one of ...

Mutant yeast reveals details of the aberrant genomic machinery of children's high-grade gliomas

July 18, 2017
St. Jude Children's Research Hospital biologists have used engineered yeast cells to discover how a mutation that is frequently found in pediatric brain tumor high-grade glioma triggers a cascade of genomic malfunctions.

Late-breaking mutations may play an important role in autism

July 17, 2017
A study of nearly 6,000 families, combining three genetic sequencing technologies, finds that mutations that occur after conception play an important role in autism. A team led by investigators at Boston Children's Hospital ...

Newly discovered gene variants link innate immunity and Alzheimer's disease

July 17, 2017
Three new gene variants, found in a genome wide association study of Alzheimer's disease (AD), point to the brain's immune cells in the onset of the disorder. These genes encode three proteins that are found in microglia, ...

0 comments

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.