RAF induced vascular endothelial growth factor augments Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) infection / by Khalief Edward Hamden.
| Author/creator | Hamden, Khalief Edward author. |
| Other author | Akula, Shaw M., degree supervisor. |
| Other author | Kalmus, Gerhard W., degree supervisor. |
| Other author | East Carolina University. Department of Biology. |
| Format | Theses and dissertations |
| Production | 2004. |
| Description | 67 leaves : illustrations ; 28 cm |
| Supplemental Content | Access via ScholarShip |
| Subjects |
| Summary | Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) is etiologically associated with Kaposi's sarcoma (KS) as well as other tumors. Vascular endothelial growth factor (VEGF), a mitogen that spurs angiogenesis and vascular permeability, has been implicated in the progression of KS due to its role in tumorigenesis. It has been previously shown that KSHV entry into cells and VEGF expression are enhanced by oncoprotein Raf mediated signaling. Hence, the goal of this study was to determine the direct role of VEGF in the entry of KSHV. Herein, the data demonstrate a role for VEGF and Raf in the KSHV infection of human foreskin fibroblasts (HFF). The AB-Raf:ER (BRaf that is conjugated to an estrogen receptor) expression in HFF was conditionally activated by treating cells with P-estradiol. (3-estradiol stimulated HFF/AB-Raf cells express elevated concentrations of endogenous VEGF which supported increased levels of recombinant green fluorescence protein encoding KSHV (rKSHV.I52) infection. Furthermore, rKSHV.152 infection of p-estradiol stimulated HFF or EIFF expressing a weaker form of B-Raf could be enhanced to levels comparable to that of HFF/AB cells by pretreating cells with soluble VEGF. Conversely, VEGF expression and infection efficiency typically observed in P-estradiol stimulated HFF/AB-Raf could be lowered significantly by treating with VEGF si-RNA. Enhancement of the KSHV infection occurred in HFF cells transfected with human VEGF121. Results of this study show that the Raf induced VEGF expression has a major role in the enhancement of KSHV entry at a post-cell attachment stage. These results document an interaction between Raf and VEGF expression which may be important in KSHV associated pathogenesis. |
| General note | Presented to the faculty of the Department of Biology. |
| General note | Advisor: Shaw M. Akula |
| General note | Advisor: Gerhard W. Kalmus |
| Dissertation note | M.S. East Carolina University 2004 |
| Bibliography note | Includes bibliographical references (leaves 54-65). |
| Genre/form | dissertations. |
| Genre/form | Academic theses. |
| Genre/form | Academic theses. |
| Genre/form | Thèses et écrits académiques. |