Genetic diversity of HHV8 subtypes in South Africa: A5 subtype is associated with extensive disease in AIDS‐KS

Abstract

Human herpes virus 8 (HHV8) is the etiological agent of all forms of Kaposi's sarcoma (KS). Six major subtypes (A-F), based on genetic variability of open reading frame (ORF)-K1, have been identified. Numerous studies point to differing tumorigenic and pathogenic properties of the HHV8 subtypes. The study objectives were to determine the HHV8 subtypes and their prevalence in a cohort of clinical and histologically confirmed KS in Cape Town, South Africa, and analyze associations between the different subtypes and clinical presentation of KS. Clinical records were prospectively reviewed to extract clinical presentation; demographic data were retrospectively collected and tissue biopsies were taken for ORF-K1 subtyping. Eighty six patients were subtyped; 81 AIDS (acquired immune deficiency syndrome)-KS and 5 African endemic-KS. Subtype A5 (42/86) and B2 (16/86) predominated. B1, B3, A1 and A4 subtypes were identified in 10/86, 9/86, 4/86 and 1/86 patients, respectively. A5 and B subtypes were found in African blacks and individuals of mixed ancestry, while subtypes A1 and A4 were found only in whites and individuals of mixed ancestry. Subtype A5 was associated with >10 KS lesions at presentation in the AIDS cohort (adjusted OR: 3.13; CI: 1.02-9.58). Subtypes A1 and A4 combined were less likely to be associated with poor risk tumor extension (P = 0.031) and A1 was associated with lower likelihood of lower limb involvement (P = 0.019). In conclusion, these results indicate that subtype A5 and B predominate in South Africa and A5 may be associated with more extensive disease.

Genotypic distribution of HHV-8 in AIDS individuals without and with Kaposi sarcoma

“…Although an association between HHV-8 variability and pathogenic potential has been demonstrated in some studies on classic, endemic and epidemic KS, [7–11] other studies failed to do so. [2,12,13] Such inconsistencies may be partially attributed to the lack of a standard method or protocol for HHV-8 genotyping, especially regarding the choice of targets in the HHV-8 genome and a more complete coverage of HHV-8 variants.…”

Diagnosis and Treatment of Kaposi Sarcoma

“…Genetic variability of ORF-K1 gene sequences correlates to 13 different variants of KSHV [14]. Limited evidence exists that certain KSHV subtypes may correlate with more aggressive disease or with particular epidemiological types of KS [15, 16]. …”

Nonepidemic Kaposi sarcoma: A recently proposed category

“… 4 We speculate that our patient's KS was caused by HHV-8 subtypes A5 or B, which have previously been seen in African blacks and individuals of mixed ancestry. 5 …”