BioProject

Herpesviruses are frequently co-present with bacterial infection at multiple sites within the body, including the mouth, gut, and genitourinary tract. More...

Herpesviruses are frequently co-present with bacterial infection at multiple sites within the body, including the mouth, gut, and genitourinary tract. The detection of replicating virus in these compartments prompted investigation into the relationship between bacterial infection and Kaposi’s Sarcoma-associated Herpesvirus (KSHV) reactivation. Using a cell line latently infected with KSHV, we examined the ability of crude spent media containing metabolic products from periodontal and gut pathogens to reactivate KSHV. Upon incubation with crude spent media, KSHV was reactivated and we detected the up-regulation of viral early and late genes, linear viral genomes, and virions. Furthermore, KSHV reactivation was associated with global increases in histone H3 and histone H4 acetylation, consistent with viral expression. To explore the transcriptional consequences of spent media, we compared the gene expression changes following reactivation by P. gingivalis spent medium to those of two well-established pharmacological activators of KSHV reactivation, tetradecanolyl phorbol acetate and sodium butyrate. Microarray analyses revealed a unique gene expression signature with P. gingivalis-associated reactivation. Concurrent with KSHV reactivation, P. gingivalis spent medium increased the hypoxia response. Hypoxia was associated with effects on epigenetic regulators, including down-regulation of UHRF1, a modulator of DNA methylation. Our findings demonstrate that products secreted by oral bacteria not only stimulate a hypoxia response, but also result in global changes in epigenetic modifications and modifiers. These findings suggest that epigenetic changes induced by P. gingivalis underlie the KSHV reactivation pathway. Overall design: Three-condition experiment using BCBL-1 cells, untreated vs. P. gingivalis (PG) spent media-treated, untreated vs. NaB-treated, untreated vs. TPA-treated. Biological replicates: 7 control, 2 PG, 3 NaB, 2 TPA. independently grown and harvested. One replicate per array. Please note that [1] there are 2 raw data files per sample (for 4 samples); the original gpr files from GenePix and modified txt files (missing header rows but otherwise identical data) used for analysis. [2] The gpr files for three samples (out of total 7samples) are unavailable, thus only the txt files are provided. [3] The *RG_geneavg_*.txt files contain complete normalized data including gene annotations and fold-change data [4] The 'M' column (in the *RG_geneavg_*.txt file) contains the 'normalized log2 ratio (Cy5/Cy3) representing test/reference' data included in each sample data table. Less...