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Discrepancies in the medical literature about the properties of HIV-1 reverse transcriptase (RT) could be a result of the purification method used. RT is the viral enzyme that converts viral RNA to DNA, which is then incorporated into the host DNA. The enzyme is normally created for research purposes by introducing its gene into the E. coli bacterium. Researchers compared the properties of wild type RT and an RT that contains a mutation that makes it resistant to AZT (variant T215Y) after using three different purification methods. All three forms of the T215Y RT had different properties, indicating differences at their active sites. They also differed in their stability to denaturation. The wild RT also differed in stability depending on the purification procedure used.

A few decades ago, the notion that a virus containing genes made from RNA could reproduce by making a DNA copy was positively heretical. Today, many such viruses, called retroviruses, have been found to use this 'backward' form of gene replication. All such viruses, including the notorious AIDS virus, transcribe their RNA genome onto a DNA copy through the action of an enzyme called reverse transcriptase (RT). Since such enzymes do not occur in the normal cell, it would seem that reverse transcriptase might be the ideal point at which to disrupt reproduction of the AIDS virus. For this reason, much research has studied the details of the structure and function of this very special enzyme. The current state of knowledge of reverse transcriptase is reviewed in detail by the author. Reverse transcriptase enzymes from a wide variety of viruses show great similarity, which suggests that they may have a common evolutionary origin. Although this enzyme is the most significant target of efforts to develop antiviral drug therapies, success has been far from complete. Azidothymidine, or AZT (now called zidovudine) blocks viral RT far more than host enzymes, but the AIDS virus is capable of developing resistant mutants. Ironically, although the mutations may be observed genetically, biochemists have been unable to identify precisely what alterations in the enzyme actually account for its resistance to AZT. A new set of reverse transcriptase inhibitors are being investigated, collectively called 'TIBO' compounds. Somewhat surprisingly, these substances inhibit the RT from HIV-1 virus, but not the same enzyme from HIV-2 virus. While the enzyme remains mysterious in some ways, the author expresses the belief that the tremendous effort being expended will make reverse transcriptase one of the best understood of all enzymes. This knowledge will certainly have significant impact on the development of therapeutic agents for patients with AIDS. (Consumer Summary produced by Reliance Medical Information, Inc.)