Battaglia, Jessica
(2014)
Comparison of viral titers and cytokine profiles between males and females at risk of kaposi's sarcoma development.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Human herpesvirus 8 (HHV-8) is the causative agent of Kaposi’s sarcoma- a cancerous tumor of endothelial origin. Development of KS among men who have sex with men (MSM) is
preceded by viral reactivation as determined by increasing viral antibody levels and viral load in circulating immune cells. Thus, prevention of viral reactivation should result in decreased KS incidence.
HHV-8 infection rates are not significantly different between men and women, yet the occurrence of KS is dramatically different between genders. The prevalence of KS in MSM (15-60%) is more frequent than that of heterosexual men (0-9%), and occurs even less frequently
(<1%) in the female population. Males are approximately around 13 times more likely to develop KS than women. This strong sexual bias brings up several possible factors that may explain the disparity between KS development and HHV-8 infection rates between men and women. Two of these factors are: First, a more robust natural immune response occurs in women following a primary infection, resulting in higher viral antibody titers. The presence of higher viral antibody
titers may control viral reactivation, thus reducing the risk of KS development. Second, there may be a hormonal regulation of viral reactivation. Our laboratory has found the presence of functional estrogen response elements in the HHV-8 genome and preliminary results suggest that
in the presence of estrogen, spontaneous reactivation of HHV-8 in B cells is reduced. Prevention of viral reactivation would decrease KS development and in this hypothesis, viral antibody titers would be decreased among women due to the lack of viral reactivation (compared to men). In addition, increased viral reactivation among men may result in increased levels of proinflammatory cytokines, which would further modulate their immune response.
To test the hypotheses that men and women mount differing immune responses to HHV-8 infection, HHV-8 antibody titers were determined in cohorts of men and women at risk of
developing KS. Circulating proinflammatory cytokine profiles were also analyzed between HHV-8 infected males and females to determine if levels of proinflammatory cytokines differ between genders. It is hypothesized that women will have a more robust immune response
resulting in fewer viral reactivation events while men, due to a lessened immune response will reactivate more frequently, and as a result will have higher levels of proinflammatory cytokines compared to women. The public health significance of this thesis is in regards to more effective treatments to combat or suppress KS development in males.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| Date: |
29 September 2014 |
| Date Type: |
Publication |
| Defense Date: |
6 August 2014 |
| Approval Date: |
29 September 2014 |
| Submission Date: |
21 July 2014 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
83 |
| 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: |
Examining viral titers and cytokine profiles of males and females who are infected with HHV-8, and attempting to determine why males develop KS much more frequently than females. |
| Date Deposited: |
29 Sep 2014 20:06 |
| Last Modified: |
13 Mar 2019 18:20 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/22442 |
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