Impact of Ephrin Receptor A2 polymorphisms on KSHV infectivity – Dr Schafer
Dr Georgia Schäfer
Title of the project
The impact of Ephrin Receptor A2 polymorphisms on KSHV infectivity and Kaposi’s Sarcoma incidence and severity in HIV/AIDS patients in South Africa
With continuously increasing incidence rates over the past 30 years, Kaposi’s Sarcoma (KS) is now the most common AIDS-related malignancy world-wide. lt is caused by the Kaposi’s sarcoma-associated herpes virus (KSHV) which infects endothelial cells via the recently identifieed ephrin receptor tyrosine kinase A2 (EphA2). This receptor is expressed on human endothelial cells and plays a key role in KSHV uptake and infection through the coordination of downstream signalling and endocytosis. The aim of the proposed study is to comprehensively characterize the role of polymorphisms in the EphA2 receptor in KSHV infection and in the incidence and severity of KS.
Patients enrolled in this study will be HIV/AIDS-positive that are KSHV-negative, or that are KSHV positive presenting with high or low severy KS or no KS. The sequency of the EphA2 receptor protein coding region and the promoter region will be determined using genomic DNA isolated from blood samples of the different patient groups. Thereafter, an association between the identified EphA2 receptor variants and KSHV presence, KS incidence and KS severity will be determined. In addition, parameters such as KSHV copy number in saliva and in KS lesions will also be determined and their association with EphA2 receptor polymorphism and impact on KS incidence and severity will be analyzed.
This research is expected to determine whether any EphA2 receptor variants are associated with KSHV infectivity, with KS incidence and/or with KS severity. This research will define risk groups for KSHV infectivity and/or KS incidence and severity based on EphA2 receptor polymorphism and broaden our understanding of KS development. Furthermore, this study can also provide diagnostic and prognostic tools for KS and indicate whether the EphA2 receptor can be a therapeutic target for prevention and treatment of KS.