CURRENT treatments for HIV infection work by stopping the virus from reproducing in cells it has infected. But there may be a better way, namely stopping those cells getting infected in the first place. That is the route proposed by Cameron Abrams and Irwin Chaiken of Drexel University in Pennsylvania. As they describe in this month’s Antimicrobial Agents and Chemotherapy, they have found a way to blow the virus up.
Unlike many viruses, HIV has a fatty outer membrane similar to that surrounding a living cell. The crucial insight Dr Abrams and Dr Chaiken had was that this membrane probably acts like a balloon—in other words the pressure inside it is greater than the pressure outside it. That means it can be burst, which is what they believe provides the driving force by which a virus injects its genetic material into a cell in order to infect it.
That process starts with the fusion of spikes made of a protein complex known as Env (short for envelope), that are dotted over the viral membrane, with another protein, CD4, which is found on the surface of certain immune-system cells called T-cells. Thus attached to its prey, a virus is able to inject its genetic material into the T-cell, take it over, and turn it into a factory for the production of more viruses.
The process of fusion is well understood; that of injection less so. But Dr Abrams and Dr Chaiken suspected what is happening is a controlled and directed bursting of the balloon that forces the genetic material through the T-cell’s membrane. They therefore reasoned that if they could burst the balloon prematurely, they would have a way of destroying HIV before it could infect anything—a potentially powerful treatment. That meant making what was, in essence, a molecular pin.
In fact, they made two such pins, which they called dual-acting virucidal entry inhibitors (DAVEIs). They did this by combining yet-further proteins known to like attaching themselves to Env spikes with other proteins they hoped would trigger the fusion mechanism and thus cause the viral balloon to burst. And it worked. When mixed with a suspension of viruses, the DAVEIs duly popped them.
It is a long way from this observation to a medicine. First, the mechanism would have to be shown to work in living creatures—especially human beings—and to do so without significant side effects. Then, ideally, it would be improved by designing a molecular pin that could be manufactured chemically, rather than being based on proteins and thus having to be turned out by living cells in bioreactors.
If such a medicine could be created, its most obvious use would be to stop HIV getting into someone in the first place, by incorporating it into vaginal rings. If sufficiently safe, though, it might also be used in those with established infections.