Kicking up an extinction

Animated HIV. Credit: Teresa Larsen, the Foundation for Scientific Literacy.

Scientists have demonstrated that viruses, such as HIV, that rely on RNA rather than DNA to carry their genetic code, can be driven to extinction by treating infected cells with a chemical that makes them mutate.

RNA viruses are naturally subject to high mutation rates when they replicate, because they lack the proofreading skills of DNA-based life forms. This is usually to their advantage because when you're infected with an RNA virus its frenzied mutations allow it to change quickly and so evade the immune system. This partly explains why there is yet no equivalent of antibiotics for treating viral diseases, such as flu and AIDS.

If the virus is given an extra kick so that its mutation rate spirals out of control, then it will quickly reach a point where it is too much of a mutant to replicate at all. Pedro Lowenstein of Cedars-Sinai Medical Center/UCLA, Los Angeles, USA and Ana Grande-Perez and Esteban Domingo from the Centro de Biologia Molecular at the University Autonoma of Madrid (UAM), Spain and colleagues have now found that they can use this mutation frenzy to drive an RNA virus to extinction by making it mutate so rapidly that its replication fails. A chemical to give a virus this kick could ultimately become a standard drug for treating RNA viruses.

	Manfred Eigen

Lowenstein and his team have studied the lymphocytic choriomeningitis virus (LCMV), a model RNA virus that affects mice and humans. They treated an infection with the mutagenic compound 5-fluorouracil (FU). With increasing dose of FU, the virus was driven to extinction and cells recovered from the infection.

In a companion paper from Nobel laureate Manfred Eigen of the Max Planck Institute for Biophysical Chemistry in Goettingen, Germany, the Lowenstein's results are discussed in terms of error catastrophe. "[The work shows that] theory cannot remove complexity, but it shows what kind of "regular" behavior can be expected and what experiments have to be done to get a grasp on the irregularities," says Eigen, "This is more true in biology than in any other field of the physical sciences." He adds that Lowenstein and others have opened up a new way to tackle viruses, "namely not by inhibiting their replication but rather by favoring it with an increased rate of mutation." Much experimental work needs to be done to demonstrate the proof of principle for each type of virus but rather than evolution, normally associated with pathogen resistance, being our enemy, it might be possible to make it our ally.

Lowenstein et al., Proc. Natl. Acad. Sci. USA, Vol. 99, Issue 20, 12938-12943

Eigen, Proc. Natl. Acad. Sci. USA, Vol. 99, Issue 21, 13374-13376^*

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