Comparison of epigenetic profiles of human oral epithelial cells from HIV-positive (on HAART) and HIV-negative subjects

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 c...

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Published inEpigenetics Vol. 8; no. 7; pp. 703 - 709
Main Authors Ghosh, Santosh K., McCormick, Thomas S., Eapen, Betty L., Yohannes, Elizabeth, Chance, Mark R., Weinberg, Aaron
Format Journal Article
LanguageEnglish
Published United States Landes Bioscience 01.07.2013
Subjects
Antiretroviral Therapy, Highly Active
Brief Report
Cell Proliferation
Cell Separation
Cell Wall - chemistry
DNA (Cytosine-5-)-Methyltransferase 1
DNA (Cytosine-5-)-Methyltransferases - metabolism
DNA Methylation - genetics
Epigenesis, Genetic
Epithelial Cells - metabolism
Epithelial Cells - pathology
Epithelial Cells - virology
Fusobacterium nucleatum - metabolism
HIV Seropositivity - drug therapy
HIV Seropositivity - genetics
HIV Seropositivity - virology
Humans
Mouth - metabolism
Mouth - pathology
Mouth - virology
DNMTs
HDAC-1
HIV
oral epithelium
hBD-2
HAART
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Summary: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.
Bibliography:ObjectType-Article-2
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ISSN:1559-2294
1559-2308
1559-2308
DOI:10.4161/epi.25028