DNA Methylation AIDS HIV Latency

Current drug therapies inhibit replication of the human immunodeficiency virus (HIV). In patients undergoing these therapies, the amount of HIV is reduced to an undetectable level and HIV-related disease subsides. However, stopping antiviral drug therapy results in the quick return of HIV and of disease. One reason for this is latently infected cells, in which virus replication is temporarily halted. When drug therapy is stopped, virus from these latently infected cells can resume infection and spread to other cells in the patient, resulting in the return of disease

One of the world's most elusive viruses is an expert at maintaining a low profile, laying dormant in CD4+ cells even during highly active anti-retroviral treatment (HAART). A team of American and Swedish researchers found that the virus might be using DNA methylation as a cloak.

Hypermethylated CpG islands flanking the HIV transcription site attract methyl-CpG binding domain protein 2 (MBD2) -- an endogenous host protein – which in turn recruits histone deacetylaces and other enzymes to shut down transcription.

Using 5-aza-deoxycytidine (Aza-CdR) to strip the DNA methylation at these island allowed researchers to reverse the transcriptional block and reactivate HIV right out of hiding, indicating that Aza-CdR might be a great complement to other antiviral therapies. So there’s hope for flushing out the reservoir, clearing patients of HIV-1, and letting them live a drug free life. Wouldn’t Nancy Reagan be proud?

See all the HAARTening details at PloS Pathogens June 2009.