Genotypic characterization of Kaposi's sarcoma-associated herpesvirus in asymptomatic infected subjects from isolated populations

Abstract

Molecular epidemiological studies of Kaposi's sarcoma-associated herpesvirus (KSHV) have concentrated on characterization of viral strains in tumour biopsy samples from Kaposi's sarcoma (KS) patients, mostly obtained in the United States and Europe. Tumour biopsies are a convenient source of viral DNA, as they have a high viral load compared to peripheral blood. However, sequences obtained from biopsies may not be representative of viral strains in asymptomatic subjects and information on ethnicity is often not available. Here, a population-based approach has been used to study the molecular and seroepidemiology of KSHV in isolated populations in Ecuador and Botswana. Amerindians in Ecuador had a variable prevalence of KSHV and all strains characterized were of subtype E, based on K1 sequencing. All Amerindian strains had predominant (P)-type K15 alleles and had sequences in both T0.7 and ORF 75 that appeared to be characteristic of these strains. The prevalence of KSHV in two ethnic groups in Botswana was extremely high. K1 sequences from both Bantu and San subjects were mostly of subtypes B and A5, which are typical of African KSHV strains, but the sequence from one San subject did not cluster with any known subtype. Considerable heterogeneity was seen in the T0.7 and ORF 75 genes in the San subjects and one had a minor (M)-type K15 allele. The heterogeneity of the KSHV strains found in these subjects from Botswana contrasts with the homogeneity of KSHV strains in Amerindians, reflecting differences in the evolutionary history of these populations.

Ugandan Kaposi’s Sarcoma-Associated Herpesvirus Phylogeny: Evidence for Cross-Ethnic Transmission of Viral Subtypes

“…Sample HKS22, from a Bantu Gisu patient, clusters with clones K1-43/Berr (from France) and San2 (from Botswana), reported by Lacoste et al [26] and Whitby et al [27] ; together, they are designated as a proposed new KSHV subtype F. HKS22 is characterized by a unique combination of minority residues in the putative VR* loop (residues 52-76), including singularly unique residues H-69 and S-71 ( fi g. 4 ). HKS22 also exhibits a unique combination of residues, including singular residues K-79 and S-83, in a region identifi ed as homologous to the variable region of the immunoglobin light chain and where variation differentiates KSHV subtypes [8,36,37] .…”

“…Sequences of a known subtype were included to aid subtype identifi cation: BCBL1 [32] , BC1 [33] , BCBL-R, BCBL-B, BC2, ASM72, TKS10, ZKS3 [34] , Tupi2 [7] , Ugd26 [17] , K1-21/Gbo, K1-52/Ali, K1-19/Edm [26] , SKS1 and SKS3 [8] . Three additional sequences that did not cluster with known subtypes in previous studies were also included to verify a possible new subtype: San2 [27] , K1-43/Berr and K1-8/Dem [26] . The mid-rooted tree was built by pairwise deletion: the alignment gaps were removed as needed in the course of pairwise distance computations.…”

“…Fifteen reference sequences from GenBank and published reports were included in the analysis to aid subtype identifi cation. Three additional sequences that did not cluster with any known KSHV subtypes in previous studies -two from Lacoste et al [26] , one from Whitby et al [27] -were included to verify the identity of a possible new subtype. All sequences were fi rst aligned in ClustalW [28] .…”

Evaluation of global clustering patterns and strain variation over an extended ORF26 gene locus from Kaposi's sarcoma herpesvirus

“…The designation N comes from the SALN6 and SALN7 samples, which were among the six samples originally described as having N subtype ORF75 genes by Alagiozoglou et al (Alagiozoglou, et al, 2000). Five of the six samples within the subgroup designated Q also came from South Africa and are closely related to both the K and R groups, except for an additional change at 1122 G to T. The designation Q is based on that used previously for a novel clustered subtype exemplified by SAPB1, SAKS29, SAKS33 and SAKS35 within the T0.7/KAP gene locus (Zong, et al, 2002;Whitby, 2004). The latter shows considerably greater divergence from the A pattern than do the B, R, M or N patterns.…”

Seroprevalence of Kaposi Sarcoma–associated Herpesvirus and Other Serologic Markers in the Brazilian Amazon

“…KSHV seroprevalence is low (<5%) in most Western populations (1) and reaches 50% in some African populations (2), mirroring KS incidence rates (3). However, the highest KSHV seroprevalences worldwide (>80% in adults) have been reported in Amerindian tribes from the Amazon regions of Brazil (4,5) and Ecuador (6), despite the apparently low KS incidence in these populations (7). KSHV is thought to be transmitted through saliva between young siblings in disease-endemic areas such as French Guiana (8) or Africa (9), whereas sexual transmission in low-prevalence countries occurs within risk groups such as men who have sex with men (10).…”