This study examined the mechanisms by which Kaposi's Sarcoma associated Herpesvirus (KSHV) reactivates from latency in oral epithelial cells. The researchers exposed latently infected BCBL-1 cells to treatments that induce reactivation, including TPA, sodium butyrate, and Porphomonas gingivalis spent media. They found that TPA and P. gingivalis induced distinct gene expression profiles, suggesting P. gingivalis induces reactivation through a novel mechanism different from TPA. This supports the hypothesis that butyrate released by P. gingivalis can induce viral reactivation from latency in vivo in the oral cavity.

1. 3857 Determinants of KSHV Reactivation using a Viral pathogenesis based Microarray
L.M. DOMINICK, V.G. LENTCHITSKY, and J. WEBSTER-CYRIAQUE, University of North Carolina, Chapel Hill, USAOur laboratory has
established that both latent and lytic forms of Kaposi's Sarcoma associated Herpesvirus (KSHV) are present in oral epithelial cells.
Objectives: The objective of this study was to develop methods to distinguish the mechanism by which KSHV reactivates from latency
in the oral cavity in vivo. It is hypothesized that butyrate released by periodontal pathogens such as Porphomonas gingivalis induce
viral reactivation from latency. Analyses of differential gene expression should then determine whether patterns of gene expression
induced by P.gingivalis is similar to that of protein kinase C driven reactivation observed with the inducing agent 12-O-
tetradecanoylphorbol-13-acetate (TPA), or histone deacetylase inhibition similar to sodium butyrate (n-bu). Methods: Latently KSHV
infected BCBL-1 cells were exposed to 25ng/ml TPA, 3mM n-bu, P. gingivalis spent media or were left untreated. RNA was extracted
from cells after 48 hours of treatment as well as from the uninfected lymphoid BJAB cell line. cDNA was synthesized, labeled with CY
dyes and hybridized to a novel microarray containing 20,000 human genes and temporally regulated viral genes from distinct stages of
the infectious cycle (immediate early, early, late, and latent) of each known human herpesvirus. Induction of viral replication was
confirmed by detection of lytic gene products on the array, reverse transcriptase PCR, and by immunofluorescence detection of lytic
antigen expression in the cultured cells. Results: We determined that the expression profile of cellular genes involved in signal
transduction, cell cycle, immune regulation and cell adhesion during viral replication induced by TPA was distinct from that induced by
the addition of P. gingivalis. Conclusion: These results support P. gingivalis as an inducer of gamma herpes viral replication, and suggest
this novel mechanism of viral induction is central to viral reactivation in the oral cavity in vivo. Studies supported by R03 DE14444-01S.
latres_dominick@dentistry.unc.edu
Seq #388 - Microbial Pathogenesis and Inhibition
10:15 AM-11:30 AM, Saturday, 13 March 2004 Hawaii Convention Center Exhibit Hall 1-2
Back to the Oral Medicine & Pathology Program
Back to the IADR/AADR/CADR 82nd General Session (March 10-13, 2004)
https://iadr.confex.com/iadr/2004Hawaii/techprogram/abstract_47204.htm