In vivo, in vitro, and in silico analysis of methylation of the HIV-1 provirus

HIV-1 latency is a barrier to overcome in the effort to fully eradicate the virus from infected individuals using highly active anti-retroviral therapy (HAART). Therefore, the study of the mechanisms underlying the establishment and maintenance of HIV-1 latency are vital to achieving a cure. Transcriptional repression of the viral promoter is the major cause of HIV-1 latency. DNA methylation of genomic regions known as CpG islands (CpGIs) is a well-established transcriptional regulatory mechanism, and the HIV-1 provirus contains several conserved CpGIs including two that are located within the viral promoter region. The study of these CpGIs in both in vitro and in vivo models of HIV-1 latency using the technique of bisulfite-mediated methylcytosine mapping has led to their identification as factors that contribute to the maintenance of HIV-1 latency. Here, we discuss the identification of CpGIs within the HIV-1 provirus and the study of their differential methylation patterns in several HIV-1 latency models using bisulfite-mediated methylcytosine mapping.