Reawakening the dormant HIV-I virus with arsenic and then killing it before it can do any harm: it may sound like the plot of a murder mystery with a genetic twist, but this is actually a potential new approach to the fight against AIDS. It has come about as a result of a study carried out at the International Centre for Genetic Engineering and Biotechnology in the Trieste AREA Science Park, published this week by the journal Cell Host & Microbe.

The research was carried out by Marina Lusic, Bruna Marini and other researchers in the ICGEB Molecular Medicine Group led by Mauro Giacca, together with Roberto Luzzati, of the Trieste University Hospital Medical Science Department. It demonstrates how the virus enters a state of functional latency that makes it insusceptible to treatment once it has entered the DNA of infected patients. In particular, the researchers from Trieste discovered that HIV-1 replication is turned off by certain bodies present in the nucleus that are made up of a protein known as PML. The study found that when the protein PML is destroyed, HIV-1 replication can resume, thus making the virus susceptible to drugs.

Reactivation occurs in a surprisingly simple way by treating the infected cells with arsenic, a drug already used in traditional Chinese medicine. Arsenic-based compounds could therefore be used for a "shock and kill" treatment strategy that involves stimulating (shocking) latent viruses and then reactivating them in order to eliminate (kill) all the cells that harbour the viral genome, using drugs that are already available to us.

"We are really enthusiastic about our discovery, especially the possible knock-on treatment implications - emphasised Marina Lusic. The mechanism we have elucidated explains the molecular bases of '"HIV latency", a phenomenon that has indirectly made it impossible to treat the disease pharmacologically. The protein we discovered, which is responsible for masking the HIV in the infected cell genome, could become an easy therapeutic target for drugs that are already clinically available for the treatment of certain types of leukaemia. Further in-depth clinical and preclinical research is nevertheless still necessary before extending the benefits offered by the molecule at in vitro cellular level to patients."

Cell Host & Microbe is accompanying the paper on the discovery with an editorial that emphasises its importance as part of the thrust to develop new treatments designed to wipe out the infection permanently. We must remember that AIDS kills nearly 2 million people a year, mainly in Africa, out of some 35 million individuals infected throughout the world. The mortality rate is much lower in Europe and the United States, where an expensive cocktail of drugs can be taken to halt the disease's progress by preventing viral replication. The drugs are not, however, able to wipe out the infection: once it has become part of human DNA, HIV-1 eludes any treatment currently on the market.

Further information:

Marina Lusic, tel. 040 3757375, lusic@icgeb.org
Mauro Giacca, tel. 040 3757324, giacca@icgeb.org