August 19, 2004

Science

The Virus Hijacker
By Richard Hollingham

With conventional treatments failing to do more than slow the spread of HIV, researchers are trying to fight fire with fire.

IF YOU’RE GOING to come up with a potential treatment for Aids, the International House of Pancakes is as good a place as any. Who knows, one day the name “Leor Weinberger” might be displayed on a plaque beside the syrup.

Weinberger, a researcher at the University of California in Berkeley, was having breakfast with a colleague. They were contemplating the failure of conventional therapies to get to grips with HIV. “The vast majority of scientists don’t believe it’s possible to eliminate the virus or to develop a protective vaccine,” he says. So he got to thinking of an entirely different approach: rather than destroying the virus, try instead to live with it. The result of his research is the design for a genetically modified virus that he hopes will be every bit as pervasive as HIV.

Human immunodeficiency virus is particularly brutal and effective. The complex parasite attacks the body’s defences, gradually weakening the ability to fight off disease. Every day 14,000 people worldwide are infected with HIV and almost two million, of the 42 million carrying it, will die before the end of the year.

It is not the virus that will eventually kill them. Once the immune system becomes depleted beyond a certain critical level, the victims develop Aids (acquired immune deficiency syndrome). The most minor infections then become deadly, and it’s only a matter of time before diseases such as pneumonia claim lives.

At the moment, treatments are aimed at increasing the amount of time between HIV infection and the onset of Aids. The drugs used are fearsomely toxic as well as expensive. Although these anti-viral treatments kill many of the HIV strains, others survive, mutating and spreading until the drugs are no longer effective. Medicines keep patients alive longer but are by no means a cure.

Only one thing comes close to matching HIV for deadliness, and that’s another virus. What is needed is a virus that uses HIV as its host. Weinberger has termed his creation a “parasite of a parasite”.

“HIV is a parasitic virus because it uses cells of the human immune system to replicate itself,” says David Schaffer, who worked with Weinberger. “The synthetic virus is identical to an HIV particle except that the harmful genetic material is replaced with an anti-HIV cargo.”

But building an entirely new virus isn’t easy. Fortunately, the researchers have been able to try out their ideas on a sophisticated computer model. They started by simulating what happens when the immune system is attacked by HIV. It’s not pretty: the body of an infected individual is pumping out around 10 billion new viruses every day, so it’s hardly surprising that anti-viral drugs are proving ineffective.

Building on this information, the researchers have been able to design a new virus that interferes with the process. The re-engineered virus looks exactly like its target: a sphere covered in spikes, rather like a “mine” used to destroy ships. What’s clever is that it doesn’t destroy HIV. Instead, just as HIV hijacks a cell, it hijacks HIV, stealing some of its components. “HIV uses the cell as a factory, our virus uses HIV as a factory,” says Weinberger.

The results in computer simulations have been impressive; the new virus significantly slowed the rate of HIV replication. But there is a downside. The synthetic virus must not entirely eradicate HIV because it needs it to survive. “We can’t make the virus too good,” Weinberger admits.

The upshot is that anyone who might one day be treated with this “good” virus would still carry the “bad” one as well. But with both viruses in the bloodstream the host would no longer develop Aids. If a carrier infected someone else with HIV — through unprotected sex, for example — they would also infect them with the new virus. As HIV spreads, so would the new virus. Anyone spreading the disease would also be spreading the “cure”. The outcome? A man-made virus passing through the population. Not surprisingly, this might alarm some people.

Science fiction is full of instances of sinister boffins playing God who create dangerous viruses which, when unleashed, devastate the world’s population. From 12 Monkeys to The Andromeda Strain there are countless warnings about meddling with technology that we don’t understand. Before any artificial virus is allowed to spread freely, the scientists would need to be sure they had got it right. Once out there it will be impossible to control — any mistake and it will be too late.

“I’m apprehensive,” admits Adam Arkin from the Lawrence Berkeley National Laboratory, the leader of the research team. “We are 99.99 per cent certain nothing bad will happen, but you don’t want to use a treatment like this until your understanding is good enough.”

Apart from any ethical and moral issues, there are plenty of things that could go wrong — ranging from the new virus becoming ineffective over time to genetic mutations making it even more dangerous than HIV.

The scientists in California are taking things very slowly. With the computer simulations complete, they have moved on to controlled experiments on real viruses in a test tube. So far the results are encouraging. Nevertheless, it will take many years before the genetically modified virus is allowed anywhere near a human being.

But would it ever be unleashed on the world? “The chance to use such a thing is governed by how critical the need is,” says Arkin cautiously. It would take a brave government to sanction such a treatment — but with the burgeoning HIV infection rate, particularly in Africa, it might become the only option.

“In regions of the world where conventional anti-HIV drugs are not widely available, a one-shot therapy virus that can hop between patients could be an advantage,” says Schaffer.

Even if this particular therapy never sees the light of day, it represents one of the first steps in a whole new area of science — “synthetic biology”. Other scientists have already created real viruses, albeit much simpler than HIV.

Arkin is excited by the potential for designing new forms of life, programming particular functions into genetic material for our benefit. “We aim to deliver molecules in a controlled way into the body. This field is going to be huge.”

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