Joachim Hauber: Driving HIV out of its hideaway

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Joachim Hauber is a professor at the Heinrich Pette Institute in Hamburg, and has been researching HIV for 20 years. Quelle: Hauber/ HPI

26.03.2008  - 

"This is a special thrill: If we succeed in finding a new treatment for HIV with one of our approaches, then that would be an unbeatable feeling!” Joachim Hauber, a professor at the Heinrich Pette Institute for Experimental Virology and Immunology at the University of Hamburg has dedicated his entire life as a researcher to a single goal: Combating the AIDS pathogen. The biologist holds particular hope for one of his projects, which may yet lead to the development of a new weapon against HIV. He has found a method – at least in the laboratory – of tracking down, detecting and destroying the virus in its favourite hiding place. With financial support from the German Federal Ministry for Education and Research (BMBF), he is now aiming to develop a therapy.

The hideout of the human immunodeficiency virus (HIV) is the patient’s genetic material. Once there, it integrates its DNA into the infected cells’ own genome. As long as the virus genome remains inactive, the infected cells behave as normal. The immune system fails to recognise the dormant virus, meaning that it cannot attack the infection. Previously available therapies are able to keep the virus in check, but are not able to remove it entirely, as long as it remains in this hiding place. This is also why there is currently no cure for AIDS (Acquired Immune Deficiency Syndrome) which can start after an infection with HIV. While doctors have available a number of medicines to help HIV-infected patients to live a long and pain-free life, no cure exists that can drive the insidious virus from the body – because it is so well hidden.

This animation explains how HIV proliferates.Quelle: youtube.com

As early as 1986, shortly after Hauber had finished his doctoral thesis, the biologist began his research into HIV. His first forays into this very new area of research were made as a post-doctoral fellow at the Hoffmann-La Roche Institute of Molecular Biology in the State of New Jersey. Today, these many years of experience have paid off. "There are not many German basic researchers with a long background in HIV research," says the now 52-year-old, with a little pride.

His work is driven by a clear goal. "It is our vision to drive the virus out from the cells and from the patient completely,” says Hauber. As the biologist reported in June 2007 in Science magazine (2007, vol. 316, p.1912-1915), he has already succeeded in the laboratory with individual cells. "Nobody has been able to do this before," recalls Hauber. With his experiment, which also involved the Max Planck Institute for Molecular Cell Biology and Genetics in Dresden, the German scientist created rippled of excitement in the scientific world. For the first time, a cure for HIV seems possible – at least theoretically. "On the other hand, perhaps such a cure will never be found," says Hauber, who is cautious not to raise hopes to high. The biologist has been involved with AIDS research long enough to have lived through a series of disappointments. "Many new therapeutic approaches ultimately fail because of the drastic side effects. But it would nevertheless be fantastic if our radical new approach really worked," he says.

Molecular tricks turned against the virus

In the sensational experiment, the scientific group led by Hauber used a molecular trick that is often applied in basic genetic research. There are molecules that can identify a particular gene sequence in the genome. Moreover, once they have located this sequence, they then go on to cut out the DNA. Because the molecules are thereby able to reorder the genes – to recombine them – they are known as recombinases.

In order to cut out HIV from the human genome, the researchers had to find a recombinase that is able to exclusively detect HIV genetic material. No such substance was known to exist at the time. What was known however was that a specific recombinase was able to respond to a very similar sequence. Hauber’s researchers would still have to go clear many hurdles before they could modify the protein so that it could find the virus sequences. Eventually, they succeeded: With the modified recombinase, the researchers cut the virus DNA out of a cell, after which the cell itself destroyed the extract. The cell was then virus-free.

Hauber now wants to develop an AIDS therapy using this technique. He triumphed in the GO-Bio competition of the German Federal Ministry of Education and Research (BMBF) with his plan to create a company to commercially drive forward such a therapy (more...). He will now be receiving funding of up to one million euros over six years. Hauber has no intentions of becoming directly involved with the company – this is a task he will be leaving to colleagues. "I am the driving force, but the firm is an opportunity for the younger members of my team”.

Gene therapy for blood stem cells

However, a functioning HIV therapy is still a long way off. The greatest hurdle lies in bringing the recombinase to the exact location where they can get to work; namely, inside the infected cells. This can’t be achieved using a syringe or tablet, because the large nature of the recombinase molecules means that they cannot break through the cell membrane. Nevertheless, Hauber has an idea as to how it could work: The infected cells could be encouraged to produce the recombinase themselves. In order to do this, he would like to genetically modify all the cells affected by the virus.

HIV infects only a certain type of white blood cell. These do not reproduce themselves, but are produced by blood stem cells. The plan is now to take blood stem cells from an HIV-infected patient, insert the recombinase gene, and then return the cells to the patient with an injection. Hauber thinks that there are reasons to be optimistic: "We want to bring down the quantity of infected cells with this process, in the hope that an improved immune system will be able to attack the remaining infection. This could one day bring about a cure for HIV-infected individuals."
Hauber is driven by more than just scientific ambition. Educating others about AIDS is also of great interest to him. "Recently, even in Germany, the number of new infections has begun to rise again" - a matter of great concern to the scientist, "because many seem to think that an effective treatment actually exists." Hauber is attempting to counteract such misconceptions, and gives talks in schools and adult groups and forums about the dangers of the AIDS pathogen. As Hauber knows: "Education is very important”.

Author: Ragnar Vogt