Genetic diversity and phylogeographic analysis of human herpesvirus type 8 (HHV-8) in two distant regions of Argentina: association with the genetic ancestry of the population

Background: The genetic diversity of persistent infectious agents, such as HHV-8, correlates closely with the migration of modern humans out of East Africa which makes them useful to trace human migrations. However, there is scarce data about the evolutionary history of HHV-8 particularly in multiethnic Latin American populations. Objectives: The aim of this study was to characterize the genetic diversity and the phylogeography of HHV-8 in two distant geographic regions of Argentina and to establish potential associations with the genetic ancestry of the population. Study design: A total of 605 HIV-1 infected subjects, Kaposi Sarcoma (KS) patients and blood donors were recruited in the metropolitan (MET) and north-western regions of Argentina (NWA). After HHV-8 DNA detection, ORF-26 and ORF-K1 were analyzed for subtype assignment. Uniparental and biparental ancestry markers were evaluated in samples in which subtypes could be assigned. Phylogeographic analysis was performed in the ORF-K1 sequences from this study combined with 388 GenBank sequences. Results: HHV-8 was detected in 24.8% of samples. ORF-K1 phylogenetic analyses showed that subtypes A (A1-A5), B1, C (C1-C3) and F were present in 46.9%, 6.25%, 43.75% and 3.1% of cases, respectively. Analyses of ORF-26 fragment revealed that 81.95% of strains were subtypes A/C followed by J, B2, R, and K. Among KS patients, subtype A/C was more commonly detected in MET whereas subtype J was the most frequent in NWA. Subtypes A/C was significantly associated with Native American maternal haplogroups (p=0.004), whereas subtype J was related to non-Native American haplogroups (p<0.0001). Sub-Saharan Africa, Europe and Latin America were the most probable locations from where HHV-8 was introduced to Argentina. Conclusions: These results give evidence of the geographic circulation of HHV-8 in Argentina, provide new insights about its relationship with ancient and modern human migrations and identify the possible origins of this virus in Argentina.