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Abstract
HIV-infected subjects on highly active antiretroviral therapy (HAART) are susceptible to comorbid microbial infections in the oral cavity. We observed that primary oral epithelial cells (POECs) isolated from HIV+ subjects on HAART grow more slowly and are less innate immune responsive to microbial challenge when compared with POECs from normal subjects. These aberrant cells also demonstrate epigenetic differences that include reduction in histone deacetylase 1 (HDAC-1) levels and reduced total DNA methyltransferase (DNMT) activity specific to enzymes DNMT1 and DNMT3A. The DNMT activity correlates well with global DNA methylation, indicating that aberrant DNMT activity in HIV+ (on HAART) POECs leads to an aberrantly methylated epithelial cell phenotype. Overall, our results lead us to hypothesize that, in patients with chronic HIV infection on HAART, epigenetic changes in key genes result in increased vulnerability to microbial infection in the oral cavity.
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Acknowlegdgments
This work was supported by National Institutes of Health grants P01DE019759 (A.W.) and R01DE018276 (A.W.) and the Center for AIDS Research Proteomics Core grant P30AI036219 (M.R.C.). We thank Drs. F. Faddoul, J.R. Blakemore, E.K. Schneider, W.S. Blood and S. Alperin for providing us with human oral tissue and E. Hill, our clinical coordinator, who was instrumental in obtaining oral biopsies.
Supplemental Materials
Supplemental material may be found here: http://www.landesbioscience.com/journals/epigenetics/article/25028