Transfer RNA modifications and DNA editing in HIV-1 reverse transcription

Abstract

Reverse transcription is a central step in HIV-1 replication that represents a typical case of interplay between viral and cellular factors. HIV-1 diverts a cellular tRNA, tRNA Lys3, to prime reverse transcription. The post-transcriptional modifications of tRNA Lys3 are crucial for completion of reverse transcription. In some HIV-1 isolates, they are required for efficient initiation of (–) strand DNA synthesis, and in all strains, methylation of A58 is required to allow productive strand transfer during (+) strand DNA synthesis. On the other hand, some human cell types have evolved an innate antiretroviral mechanism by promoting extensive deamination of the (–) strand DNA during reverse transcription. In the absence of viral defence, this hyper-editing induces DNA degradation and lethal mutagenesis of the viral DNA. However, Vif, one of the HIV-1 “accessory” proteins, is able to inhibit DNA deamination by preventing incorporation of the editing enzymes APOBEC3G and APOBEC3F into the viral particles.