Comparison of Genetic Variability at Multiple Loci across the Genomes of the Major Subtypes of Kaposi’s Sarcoma-Associated Herpesvirus Reveals Evidence for Recombination and for Two Distinct Types of Open Reading Frame K15 Alleles at the Right-Hand End

摘要: Kaposi’s sarcoma (KS)-associated herpesvirus or human 8 (HHV8) DNA is found consistently in nearly all classical, endemic, transplant, and AIDS-associated KS lesions, as well several lymphomas. We have previously sequenced the genes for highly variable open reading frame K1 (ORF-K1) protein from more than 60 different HHV8 samples demonstrated that they display up to 30% amino acid variability cluster into four very distinct evolutionary subgroups (the A, B, C, D subtypes) correlate with major migrationary diasporas of modern humans. Here we extended this type analysis six other loci across genome further evaluate overall genotype patterns potential chimeric genomes. Comparison relatively conserved ORF26, T0.7/K12, ORF75 gene regions at map positions 0.35, 0.85, 0.96 revealed typical ORF-K1-linked subtype patterns, except between 20 genomes analyzed proved be either intertypic intratypic mosaics. In addition, a 2,500-bp region extreme right-hand side unique segment 45 diverged 3,500-bp sequence position 18 examined. Furthermore, these uncharacterized “orphan” sequences encompass multiexon latent-state mRNAs encoding two alleles novel ORF-K15 protein. The predominant (P) minor (M) forms are structurally related integral membrane proteins only 33% identity one another but retain likely tyrosine kinase signaling motifs may distant relatives LMP2 latency Epstein-Barr virus. M allele also physically linked distinctive adjacent locus, some cases, linkage extends far back T0.7 locus also. Overall, results suggest an original recombination event primate virus unknown source introduced exogenous ORF-K15(M) ancient form HHV8, followed by eventual acquisition C lineage P-form subsequent additional, recent transfers homologous events A B lineages well.