Sidebar: Yelling 'Jump' to a Suicidal Virus
Lawrence Loeb's laboratory has turned mutation theory upside down to force colonies of the HIV virus to self-destruct.
By using a special compound, Loeb and UW Microbiology Chair James Mullins pushed the mutation rate of HIV into overdrive, causing a kind of viral suicide that kills the population in a test tube.
Rather than try to slow mutation down—as is one theory for treating cancer—they speed up viral mutation to a frantic level where the rate of harmful mutations overtakes the helpful ones, and the entire population dies. This threshold, where the rate of mutation becomes harmful, is known as error catastrophe.
A computer simulation of mature HIV; a portion of the virus's outer layer has been cut away to show the internal structure.
HIV is part of a family of viruses known as RNA viruses that are notorious for their rapid mutation. When confronted with environmental change, the presence of so many diverse mutations is an advantage. When the human body creates antibodies to fight the virus, for example, there are always a few mutants that turn out to be unscathed and live to reproduce. This is the reason that HIV is notoriously difficult to treat. One drug cannot kill off all the diverse mutations. Some always survive.
Error catastrophe takes a different approach. Loeb and Mullins speed up the viral mutation by introducing a compound known as a nucleoside analog. This compound is a fake—the HIV cells think it is a compound it would normally use during copying of DNA, but it has been doctored to cause mutations during copying.
The mutation rates are so high that too many damaging mutations accumulate and too few viruses survive to maintain the infection. In eight out of the nine cultures treated, the HIV levels declined below measurable levels.
"Each time the virus infects a cell it introduces a few more errors," Loeb explains. "Most of the mutations do no harm. But eventually the virus accumulates so many errors that they inactivate it."
If the same chemical manipulation holds true in mice, it may mean that science has a new weapon against AIDS. One caveat, however. Even if this treatment proves practical, it will not be a "cure." It can't eliminate any dormant forms of the virus in the human body, only active forms. —Sally James
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