title: 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.
authors.affiliation: Department of Medicine, Division of Dermatology, Groote Schuur Hospital and Faculty of Health Sciences University of Cape Town, Cape Town, South Africa.
authors.forename: Thuraya
authors.initials: T
authors.lastname: Isaacs
authors.affiliation: SAMRC/UCT Receptor Biology Research Unit, Division of Medical Biochemistry and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
authors.forename: Aron B
authors.initials: AB
authors.lastname: Abera
authors.affiliation: Department of Paediatrics, Red Cross Hospital and Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
authors.forename: Rudzani
authors.initials: R
authors.lastname: Muloiwa
authors.affiliation: SAMRC/UCT Receptor Biology Research Unit, Division of Medical Biochemistry and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
authors.forename: Arieh A
authors.initials: AA
authors.lastname: Katz
authors.affiliation: Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
authors.forename: Gail
authors.initials: G
authors.lastname: Todd
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000453:epidemiology* / Q000473:pathology; D000328:Adult; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D019288:Herpesvirus 8, Human / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D017720:Molecular Epidemiology; D015995:Prevalence; D012189:Retrospective Studies; D012514:Sarcoma, Kaposi / Q000453:epidemiology* / Q000473:pathology / Q000821:virology*; D013019:South Africa / Q000453:epidemiology
keywords: HHV8; KSHV; Kaposi's sarcoma; ORF-K1; human herpes virus 8