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Sex Hormone Modulation of HHV-8 Transcription

COMPAORE, TEGWINDE REBECA (2012) Sex Hormone Modulation of HHV-8 Transcription. Master's Thesis, University of Pittsburgh. (Unpublished)

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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.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorJenkins,
Committee MemberGupta, Phalgunipgupta1@pitt.eduPGUPTA1
Committee MemberRappocciolo,
Date: 24 September 2012
Date Type: Publication
Defense Date: 28 June 2012
Approval Date: 24 September 2012
Submission Date: 10 August 2012
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Number of Pages: 71
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Infectious Diseases and Microbiology
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: Human Herpesvirus 8
Date Deposited: 24 Sep 2012 19:07
Last Modified: 24 Sep 2017 05:15


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