The influence of HIV sense and antisense transcripts on stochastic HIV transcription and reactivation

In this study, we established dozens of single provirus-infected cellular clones offering various transcriptional phenotypes of HIV. We proposed that stochastic fluctuations in HIV transcription can appear at, at least, two levels: (1) the chromosomal landscape and (2) the in situ HIV integration site. In the former case, proviruses integrating at different genomic locations demonstrated a variety of transcriptional bursting and can be classified in noise space constructed based on the parameters associated with the coefficient of variation and using a mathematical model fitting a curve of exponential decay. In the latter case, stochastic HIV transcription can be unveiled through its phenotypic bifurcation and tended to be a pure epigenetic phenomenon: the identical provirus demonstrated fluctuations in its transcription with an elevated frequency. We observed similar expression patterns between sense and antisense RNA transcripts. Notably, both HIV long terminal repeats reacted to drug stimulation and may reveal distinct behaviors. Overall, our data suggest that HIV antisense transcripts could be involved in the stochastic nature of HIV transcription.