HIV-1 RNA Editing, Hypermutation, and Error-Prone Reverse Transcription

Bourara et al. (1) reported that transcripts of the human immunodeficiency virus–type 1 (HIV-1) were subject to RNA editing in chronically infected cells. They observed multiple guanine-to-adenine (G-to-A) and cytosine-to-uracil (C-to-U) changes in several regions of the HIV-1 RNA; commonly, a G-to-A change in the untranslated leader was present exclusively in spliced HIV-1 messenger RNA (mRNA), but not in the unspliced RNA and the proviral DNA genome. Changes in the viral protein R (vpr) gene were present in spliced and unspliced HIV-1 RNA extracted from the cell, but not in the unspliced RNA genome that is packaged in virion particles. Therefore, Bourara et al. proposed that post-transcriptional mRNA-editing events occur for a subset of viral RNAs. Known editing mechanisms, however, cannot easily explain these changes in the HIV-1 genome. We here propose an alternative mechanistic model based on HIV-1 reverse transcription to explain some of the nucleotide changes.