Mechanistic Variations among Reverse Transcriptases of Simian Immunodeficiency Virus Variants Isolated from African Green Monkeys

Here we report enzymatic variations among the reverse transcriptases (RTs) of five simian immunodeficiency virus (SIV) strains, Sab-1, 155-4, Gri-1, 9063-2, and Tan-1, which were isolated from four different species of naturally infected African green monkeys living in different regions across Africa. First, Sab-1 RT exhibits the most efficient dNTP incorporation efficiency at low dNTP concentrations, whereas the other four SIVagm RT proteins display different levels of reduced polymerase activity at low dNTP concentrations. Tan-1 RT exhibited the most restricted dNTP incorporation efficiency. Indeed, the pre-steady state analysis revealed that Sab-1 RT displays tight dNTP binding affinity (K-d similar to 1-5 mu M), comparable to values observed for NL4-3 and HXB2 HIV-1 RTs, whereas the dNTP binding affinity of Tan-1 RT is 6.2, similar to 34.8-fold lower than that of Sab-1 RT. Second, Tan-1 RT Fidelity was significantly higher than that of Sab-1 RT. Indeed, Tan-1 RT enzymatically mimics oncoretroviral murine leukemia virus RT which is characterized by its low dNTP binding affinity and high Fidelity. This study reports that simultaneous changes in dNTP binding affinity and fidelity of RTs appear to Occur among natural SIV variants isolated from African green monkeys.