eprintid: 13517
rev_number: 18
userid: 819
dir: disk0/00/01/35/17
datestamp: 2012-09-24 19:07:39
lastmod: 2017-09-24 05:15:06
status_changed: 2012-09-24 19:07:39
type: thesis_degree
metadata_visibility: show
contact_email: rebecca23fr@gmail.com
item_issues_count: 0
eprint_status: archive
creators_name: COMPAORE, TEGWINDE REBECA
creators_email: rebecca23fr@gmail.com
title: Sex Hormone Modulation of HHV-8 Transcription
ispublished: unpub
divisions: sch_gsph_infectiousdiseasesmicrobiology
full_text_status: public
keywords: Human Herpesvirus 8
abstract: Human herpesvirus 8 (HHV-8) seroprevalence is similar in men and women, but Kaposi’s sarcoma (KS) is mostly seen in men, suggesting that sex hormones play a role in KS development. Previous work from our laboratory has identified potential estrogen response elements (EREs) within several regulatory genes’ promoters such as K8 (KB-Zip), ORF50 and ORF49.   The HHV-8 EREs were found to bind the alpha estrogen receptor. The functionality of the K8 EREs was demonstrated using transient expression assays.
In this study, we tested the hypothesis that estrogen modulates the transcription of HHV-8 during latency or reactivation.
     BCBL-1 cells are a B established from a pleural effusion lymphoma that is HHV-8 positive and Epstein-Barr virus (EBV) negative were used in the current study. Trex-BCBL-1 cells contain a doxycycline inducible ORF50 gene. MCF-7 cells are well studied breast cancer cell line. Production of infectious virus was determined using a TCID50 assay. Transcription of individual viral genes was measure by RT-PCR using specific primers. Measurement of cellular transcription following estrogen treatment was performed using estrogen signaling PCR arrays.
     Treatment of BCBL-1 or TRex-BCBL-1 cells with estrogen did not result in viral reactivation as measure by flow cytometry. Estrogen treatment did not prevent TPA-induced reactivation of BCBL-1 cells or doxycycline-induced reactivation of TRex-BCBL-1 cells. treatment of BCBL-1 cells with estrogen alone resulted in a decrease of constitutive viral transcription. BCBL-1 express estrogen receptor beta (compared to MCF-7 cells which express estrogen receptor alpha).Treatment of MCF-7 cells with estrogen result in an increase in transcription of cellular genes while treatment of BCBL-1 resulted in a decrease in cellular transcription.
     Our results suggest that estrogen can down-regulate both cellular and viral transcription in B cells. This down regulation may be involved in the lack of KS development in women.  
     Statement of Public Health relevance:  Reactivation of HHV-8 has been shown to be associated with the advent of Kaposi’s sarcoma. By determining the role of estrogen in the transcription of viral genes and the estrogen receptors involved, potential therapeutic target can be found. The results from these experiments will help understand the biology of HHV-8, and pathology of Kaposi’s sarcoma.
date: 2012-09-24
date_type: published
pages: 71
institution: University of Pittsburgh
refereed: TRUE
etdcommittee_type: thesis_advisor
etdcommittee_type: committee_member
etdcommittee_type: committee_member
etdcommittee_name: Jenkins, Franck
etdcommittee_name: Gupta, Phalguni
etdcommittee_name: Rappocciolo, Giovanna
etdcommittee_email: fjenkins@yahoo.fr
etdcommittee_email: pgupta1@pitt.edu
etdcommittee_email: giovannna@pitt.edu
etdcommittee_id: 
etdcommittee_id: PGUPTA1
etdcommittee_id: 
etd_defense_date: 2012-06-28
etd_approval_date: 2012-09-24
etd_submission_date: 2012-08-10
etd_release_date: 2012-09-24
etd_access_restriction: 5_year
etd_patent_pending: FALSE
thesis_type: thesis
degree: MS
citation:   COMPAORE, TEGWINDE REBECA  (2012) Sex Hormone Modulation of HHV-8 Transcription.  Master's Thesis, University of Pittsburgh.    (Unpublished)  
document_url: http://d-scholarship-dev.library.pitt.edu/13517/1/TEGWINDE_R_COMPAORE_ETD_2012.pdf