Research Projects

Kaposi’s sarcoma cancer research – Prof Arieh Katz

Kaposi’s sarcoma cancer research – Prof Arieh Katz

Prof Arieh Katz

Prof Arieh Katz

Project Title

Polymorphism in the Kaposi’s Sarcoma-associated Herpes virus G Protein-Coupled receptor gene in South Africans

Project Description

Kaposi’s sarcoma-associated herpes virus (KSHV) also called human herpesvirus-8 (HHV8) is the key cause of Kaposi’s sarcoma (KS). KS is the most common AIDS-related malignancy and is one of the most common cancers is several sub-Saharan African countries. KSHV encodes a G-protein-coupled receptor (GPCR), termed vGPCR which is a key molecule in the pathogenesis of Kaposi’s sarcoma and is a target for development of drugs for treatment of Kaposi’s sarcoma. Although this disease is more prevalent in Africa, only one vGPCR of a viral isolate from an African patient has been sequenced and it was found to differ in two amino acids from the prototype vGPCR of the Northern Hemisphere. In view of the etiological role vGPCR has in this disease, we intend to determine if there is sequence polymorphism in the KSHV vGPCR encoded protein and/or its promoter region found in South African populations and to determine the functional consequences these vGPCR variants have in KS initiation and progression in South African populations.

Non-scientific report

Kaposi’s sarcoma (KS) is the most common AIDS-related malignancy and is one of the most common cancers is several sub-Saharan African countries. This cancer is caused by a virus named Kaposi’s sarcoma-associated herpes virus (KSHV). This virus encodes a G-protein-coupled receptor (GPCR), termed vGPCR and this vGPCR is a key molecule in the development of Kaposi’s sarcoma. Although this disease is more prevalent in Africa, little is known about vGPCR encoded by the Kapsosi’s virus in South African patients.

In this project, we obtained tissue samples of the tumours from AIDS patients having KS. We isolated the genetic material (DNA) of the virus in the tumours. Thereafter, we sequenced the vGPCR gene from patient tumours and aligned them to known sequences and to each other. We have found that almost all Kaposi Sarcoma samples analysed (104 of 106 patient samples examined) had variations in the viral GPCR DNA, while the other two samples were identical to the prototype. Majority of the changes/deletions were at the DNA level only. However, a few of the changes resulted in changes in the receptor protein and 4 vGPCR receptor variants were identified. We have been studying the functional consequences of these 4 receptor variants in cell cultures and have found that the receptor variant have similar activity to the known northern hemisphere receptor. However, further studies utilizing blood cell line are required in order to determine the activity and functional consequences of the identified receptor variants.

In addition, we have subtyped the KSHV found in the South African patients by sequencing and aligning a DNA sequences of the ORFK1 which is the region used for the virus classification. Aligning the sequences obtained demonstrated that the vast majority of KHSV isolates were subtype A5 (50 samples) and B1-3 (43 samples) which are viral subtypes known to predominate in Africa. In addition, several were subtype A1, A2 and A4 which are viral subtypes that predominate in Europe and USA. Interestingly, the viruses found in 2 patients did not belong to any of the known subtypes, suggesting there are newly evolving strains. Currently based on our analyses of the viral sequences, we are investigating for possible relationship between the KSHV subtypes, vGPCR variants and clinical manifestations of KS in the different South African patients.

We have also analysed the vGPCR DNA region that controls its expression. We have found that this DNA region in viruses isolated from 80 of the 86 sample analysed are different from the known Northern hemisphere samples. We are now examining if these changes can affect the expression level of the vGPCR receptor and as such may affect disease initiation and progression.

Abstracts

  • Investigating polymorphism in the Kaposi’s sarcoma associated herpes virus G-protein coupled Receptor gene in South African Kaposi’s Sarcoma Tumors. EMBO Conference, Cellular Signaling & Molecular Medicine, 25-29 May, 2012 Cavtat-Dubrovnik, Croatia.
  • Polymorphism in the Kaposi’s sarcoma associated herpes virus G-protein coupled Receptor gene in South African Kaposi’s Sarcoma Tumors. The Biochemistry, Biology and Pathology of MAP kinases October 14-18, 2012 – Ma’ale Hachamisha, Israel

Conferences

  • EMBO Conference, Cellular Signaling & Molecular Medicine, 25-29 May, 2012 Cavtat-Dubrovnik, Croatia.
  • The Biochemistry, Biology and Pathology of MAP kinases, October 14-18, 2012 – Ma’ale Hachamisha, Israel

 

« BACK


Do you have a question?