Challenges in Quantifying Cytosine Methylation in the HIV Provirus.

Sarah A Lamere,Christina Huynh,Antoine Chaillon,Davey M Smith,Sara Gianella

doi:10.1128/mbio.02268-18

Abstract

DNA methylation is an epigenetic mechanism most commonly associated with transcriptional repression. While it is clear that DNA methylation can silence HIV proviral expression in in vitro latency models, its correlation with HIV persistence and expression in vivo is ambiguous, particularly in persons living with HIV (PLWH) receiving antiretroviral therapy (ART). Several factors potentially contribute to discrepancies between results in the literature, including differences in integration sites, functional proviral load, sampling bias, and stochastic PCR amplification. Recent studies into genomic features of cytosine methylation sites in mammalian genes offer potentially significant insights into this mechanism. Here, we discuss the importance of these factors in the context of the HIV.

Highlights

DNA methylation is an epigenetic mechanism most commonly associated with transcriptional repression
Studies of CpG methylation in the HIV promoter from clinical samples demonstrated that this modification is inversely correlated with viremia and proviral reactivation, suggesting that CpG methylation of the HIV promoter is a regulator of latency [3]
Most HIV DNA methylation studies have focused upon these two CpG islands (CGIs), with little regard for the rest of the provirus

Summary

Introduction

DNA methylation is an epigenetic mechanism most commonly associated with transcriptional repression. Many of these limitations result from a lack of available methods for specific assessment of the replication-competent HIV reservoir in clinical samples, as well as technical challenges of studying DNA methylation in the context of HIV. Reports suggest that DNA CpG methylation silences HIV proviral expression [8].

Results

Conclusion