Systematic Kaposi-Sarcoma Herpesvirus (KSHV) genome analysis from a South African HIV- and KSHV-positive patient cohort

Thomas, Melissa

Systematic Kaposi-Sarcoma Herpesvirus (KSHV) genome analysis from a South African HIV- and KSHV-positive patient cohort

Thesis / Dissertation

2024

Publisher

University of Cape Town

Department

Division of Medical Biochemistry

Faculty

Faculty of Health Sciences

Abstract

Kaposi sarcoma herpesvirus (KSHV) is an oncogenic virus and the etiological agent of Kaposi's sarcoma, the most common AIDS-associated cancer. KSHV infection occurs primarily in Sub-Saharan Africa (SSA) where it is also associated with other pathologies such as Multicentric Castleman's Disease, Primary Effusion Lymphoma and KSHV-associated inflammatory cytokine syndrome, which also occur primarily with HIV co-infection. IN SSA most individuals ac-quire KSHV infection during childhood where it remains undetected until later in life when the burden of HIV takes its effect on the immune system. There are 6 predominant KSHV subtypes world-wide, namely A, B, C, D, E and F which are determined by the highly variable K1 region of the KSHV genome. Sequencing and characterizing the circulating subtypes in a specific geographical region assist in tracking evolutionary changes as well as malignant outcomes associated with different subtypes. The aim of this study was to determine the circulating KSHV subtypes in the Western Cape region of South Africa. A total of 57 DNA samples isolated from peripheral blood of confirmed HIV/KSHV co-infected patients were selected according to KSHV viral load (VL) (> 5 copies/10 μL) and volume (> 5 μL). Of these, 20 were successfully Sanger sequenced to determine K1 subtype. Additionally, 9 samples met the criteria for whole-genome sequencing using Next Generation Sequencing (NGS). This study produced 29 K1 sequences (20 via Sanger and 9 via NGS) of which 26 were of the A subtype, specifically A5, and the remaining 3 were of the B subtype, namely B2. These results are consistent with previous studies from the same region where a trend of high A5 and B subtypes in AIDS-KS patients were reported. ORF-K15 is another variable and lytic gene associated with KSHV subtyping (alleles M, N and P). Sequencing results of the K15 gene, revealed two P subtypes, three M subtypes and four N subtypes in our samples. These novel results from the Western Cape of South Africa point towards an interesting distribution of subtypes contributing to previous reports of K15 P and M subtypes being the most prevalent in Africa. There are limited whole-genome sequences available for South Africa, therefore these sequences provide a significant contribution to the pool of sequences available for this region.

Keywords

Medicine

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