Effects of reverse-transcriptase mutations M184V and E89G on simian immunodeficiency virus in rhesus monkeys

Mutations in human immunodeficiency virus type 1 reverse-transcriptase codo ns 89 and 184 confer inhibitor resistance and alter the mutation spectrum o f the enzyme. Six macaques were inoculated with wild-type or mutated deriva tives (E89G or E89G and M184V) of simian immunodeficiency virus macaque (SI Vmac) 239. Five of the infected monkeys maintained high virus loads; the si xth, which was infected with the E89G mutant strain, maintained viremia at a level below the limit of detection. Sequence analysis demonstrated substa ntial reversion of the E89G mutation in the animals with progressive infect ion and preservation of this mutation in the animal with controlled infecti on. A P272S mutation occurred at high frequency in the viruses containing M 184V, which did not revert. These results demonstrate that the E89G mutatio n has a significant negative impact on SIVmac fitness, whereas SIVmac beari ng M184V achieved high, sustained virus loads, perhaps with a compensatory effect of the P272S mutation.