Geographically Distinct HHV-8 DNA Sequences in Saudi Arabian Iatrogenic Kaposi's Sarcoma Lesions

Abstract

A new member of the gamma-herpesvirus family, HHV-8 (also known as Kaposi's sarcoma (KS)-associated herpesvirus), has been linked to KS and body cavity-based lymphoma. Other members of this family, eg, Epstein-Barr virus, were originally thought to have only one strain, but subsequent analysis revealed different strains correlating to cellular patterns of infectivity and geographical location. To determine whether multiple strains of HHV-8 exist, we compared DNA sequences among KS and body cavity-based lymphoma-derived HHV-8 and examined differences in HHV-8 subgroups between American and Saudi Arabian iatrogenic KS patients. Samples were analyzed by polymerase chain reaction using multiple primer sets to five different open reading frames from HHV-8, and DNA sequencing was performed. HHV-8 DNA was present in all of our KS and body cavity-based lymphoma samples by polymerase chain reaction. HHV-8 DNA was detected in each body cavity-based lymphoma sample using a majority of the primers, whereas only two primer sets consistently amplified HHV-8 DNA derived from KS lesions. DNA sequencing within open reading frames 26 and 27 indicate the existence of at least three variants of HHV-8, with the majority of iatrogenic KS patients in Saudi Arabia containing unique nucleotide changes that may define a distinct, previously unidentified subgroup we term SA, whereas those from America were of Group A or B. Thus, although the sequencing data within open reading frames 26 and 27 did not permit discrimination between patients with lymphoma versus KS disease processes, HHV-8 derived from Saudi Arabian KS lesions were shown to have a distinct nucleotide sequence not seen in any of the other clinical samples examined.

HHV‐8 subtypes in South Africa: Identification of a case suggesting a novel B variant

“…Three of these renal transplant patients, as well as two patients with African endemic Kaposi's sarcoma, had B2 type ORF-K1 genes. Distinct clustering of ORF 26 type B3/C2 polymorphisms were found in the HHV-8 genomes from Saudi Arabian renal transplant patients [Foreman et al, 1998], and they also belonged to the ORF-K1 subtype C [Poole et al, 1999]. In contrast, we identified ORF 26 type B3/C2 patterns in one patient with post-transplant Kaposi's sarcoma and two patients with the African endemic form who had A5 type ORF-K1 genes.…”

Pattern of skin cancer among Saudi patients attending a tertiary care center in Dhahran, Eastern Province of Saudi Arabia. A 20‐year retrospective study

“…Eight of 10 Saudi males diagnosed with KS had the classic type, which usually affects elderly Mediterranean men or men of eastern European descent. This is explained by the higher rates of human herpesvirus‐8 infection in countries bordering the Mediterranean basin . The two other patients were immune suppressed (AIDS and renal transplant on immune suppression), which are also two independent risk factors for developing KS …”

Detection of Human Herpesvirus 8 in Korean Kaposi's Sarcoma Cases by Polymerase Chain Reaction and In situ Polymerase Chain Reaction

“…Some studies (25,26) have revealed that there are at least three strains of HHV-8 as the result of sequence analysis in various types of KS and suggested the possibility of a geographic distribution of variants. Recently, Nicholoff et al (27) reported geographically distinct HHV-8 DNA sequences in Saudi Arabian iatrogenic Kaposi's sarcoma lesions showing a change of C~T in nucleotide 1086 and a change of G~T in nucleotide 1490. The change of C~T in nucleotide 1086 was also frequently found in our KS samples, but the other nucleotide was not included in our PCR-amplified products.…”