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

Abstract

Objective: The aim of this study was to test the relationship between Kaposi’s sarcoma-associated herpesvirus (KSHV) phylogeny and host ethnicity at the within-country scale. Methods: KSHV genomic DNA samples were isolated from 31 patients across eleven Ugandan ethnic groups. Amino acid sequences of the ORF-K1 gene were used to construct a neighbor-joining phylogenetic tree. Results: A5 and B1 variants predominated with no evidence of distinct ethnic or geographic distribution. A new K1 subtype (F) was identified in a member of the Bantu Gisu tribe and a new subtype B variant (B3) among members of the Bantu Ganda tribe. Conclusions: The phylogeny may yet be structured by host ethnicity if members of Ugandan groups have convoluted biological origins, even as they identify with single tribes. An alternative possibility is that KSHV subtype evolution may have preceded major diversification of sub-Saharan Africans into ethnicities as we know them today, with ethnic groups beginning their histories already hosting multiple subtypes. A third alternative is that horizontal transmission of multiple KSHV subtypes may have broken up vertical lineages of the virus passed down within Ugandan populations.

Genetic diversity of the Kaposi's sarcoma herpesvirus K1 protein in AIDS-KS in Zimbabwe

“…Indeed, the prevalence of subtype A5 in Zimbabwe (45%) is remarkably similar to that observed in smaller studies of other ethnic groups in diverse geographic areas in Africa: A5 was identified in 53% of 31 KS patients in Uganda (Kajumbula et al 2006) and 34% of 32 KS patients in West and Central African countries (Lacoste et al 2000). Zimbabwean A5 sequences in our study were closely related to each other and to reference sequences from distant areas of Africa with little evidence of genetic diversity.…”

“…One hypothesis to explain the distribution of K1 subtype A5 in Africa is that a prototype A5 gene was introduced into African populations through a "very rapid and recent aggressive spread" augmented by a selective advantage of the A5 allele (Hayward and Zong, 2006). Indeed, the prevalence of subtype A5 in Zimbabwe (45%) is remarkably similar to that observed in smaller studies of other ethnic groups in diverse geographic areas in Africa: A5 was identified in 53% of 31 KS patients in Uganda (Kajumbula et al 2006) and 34% of 32 KS patients in West and Central African countries (Lacoste et al 2000).…”

“…The frequency of different K1 types variants observed in the 65 Zimbabweans in our study and in 48 Ugandan patients from previous studies (Cook et al 1999, Kajumbula et al 2006, Kakoola et al 2001) were compared (Table 1). Although K1 subtypes C and F collectively represented 10% of Ugandan sequences, these subtypes were not found in Zimbabwe.…”

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

“…Additional peripheral blood mononuclear cell (PBMC) samples collected anonymously with consent for diagnostic and research analysis from KS patients at the University of Kampala in Uganda (HKS6 to HKS67 set) were also reported on previously for ORF-K1 (Kajumbula, 2006). A series of KS biopsy DNA samples from the Republic of South Africa (SAKS21 to SAKS35 set) were provided by Lee Alagiouzoglou, Lynn Morris and Fred Sitas (National Virology Institute, Johannesberg).…”

“…Nevertheless, some genomes that are identical in ORF26 differ at other loci, and linkage and recombination patterns across the entire KSHV genome can be complex. Furthermore, when all eight constant region loci plus the VIP (K1) and TMP (K15) genes are all taken into account, very few African genomes fail to show at least some chimerism Kajumbula, et al, 2006;Zong, et al, 2002). The situation is much simpler for Eurasian genomes, with only 30 to 50% showing one or more inter-subtype recombination events (Zong, et al, 2002).…”