Can Drugs Force HIV into Error Catastrophe?

RNA viruses in general and HIV in particular havea high error rate, due to their high replication rateand the error prone RNA polymerase or reversetranscriptase. It was first suggested in the 1980s byEigen, Schuster et al. at the Max-Planck-Institute forBiophysical Chemistry (Gottingen, Germany) thatRNA viruses are replicating near the error catastrophethreshold, over which they would accumulateso many errors in their genome that they wouldloose their genetic integrity, resulting in a deadvirus. Forcing these viruses over this thresholdwould result in eradication of the virus (either in vitroon in an infected individual). The first experimentalevidence of the existence of such an error catastrophethreshold was provided by Holland, Domingo,De la Torre, and Steinhauer (J Virol 1990; 64:3960-2), who could increase the error rate of thesetwo RNA viruses only 2 to 3-fold before passing thiserror catastrophe threshold. The concept was alsoneatly summarized in their recent review (Domingo& Holland. Ann Rev Microbiol 1997; 51: 151-78).