Whole-genome sequencing of Kaposi's sarcoma-associated herpesvirus from Zambian Kaposi's sarcoma biopsy specimens reveals unique viral diversity

Landon N. Olp, Adrien Jeanniard, Clemence Marimo, John T West, Charles Wood

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23 Citations (Scopus)

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent for Kaposi's sarcoma (KS). Both KSHV and KS are endemic in sub-Saharan Africa where approximately 84% of global KS cases occur. Nevertheless, whole-genome sequencing of KSHV has only been completed using isolates from Western countries-where KS is not endemic. The lack of whole-genome KSHV sequence data from the most clinically important geographical region, sub-Saharan Africa, represents an important gap since it remains unclear whether genomic diversity has a role on KSHV pathogenesis. We hypothesized that distinct KSHV genotypes might be present in sub-Saharan Africa compared to Western countries. Using a KSHV-targeted enrichment protocol followed by Illumina deep-sequencing, we generated and analyzed 16 unique Zambian, KS-derived, KSHV genomes. We enriched KSHV DNA over cellular DNA 1,851 to 18,235-fold. Enrichment provided coverage levels up to 24,740-fold; therefore, supporting highly confident polymorphism analysis. Multiple alignment of the 16 newly sequenced KSHV genomes showed low level variability across the entire central conserved region. This variability resulted in distinct phylogenetic clustering between Zambian KSHV genomic sequences and those derived from Western countries. Importantly, the phylogenetic segregation of Zambian from Western sequences occurred irrespective of inclusion of the highly variable genes K1 and K15. We also show that four genes within the more conserved region of the KSHV genome contained polymorphisms that partially, but not fully, contributed to the unique Zambian KSHV whole-genome phylogenetic structure. Taken together, our data suggest that the whole KSHV genome should be taken into consideration for accurate viral characterization.

Original languageEnglish (US)
Pages (from-to)12299-12308
Number of pages10
JournalJournal of virology
Volume89
Issue number24
DOIs
StatePublished - Jan 1 2015

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Human herpesvirus 8
Human Herpesvirus 8
Kaposi's Sarcoma
sarcoma
biopsy
Genome
Biopsy
genome
Africa South of the Sahara
Sub-Saharan Africa
phylogeny
genetic polymorphism
genomics
High-Throughput Nucleotide Sequencing
DNA
etiological agents

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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Whole-genome sequencing of Kaposi's sarcoma-associated herpesvirus from Zambian Kaposi's sarcoma biopsy specimens reveals unique viral diversity. / Olp, Landon N.; Jeanniard, Adrien; Marimo, Clemence; West, John T; Wood, Charles.

In: Journal of virology, Vol. 89, No. 24, 01.01.2015, p. 12299-12308.

Research output: Contribution to journalArticle

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abstract = "Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent for Kaposi's sarcoma (KS). Both KSHV and KS are endemic in sub-Saharan Africa where approximately 84{\%} of global KS cases occur. Nevertheless, whole-genome sequencing of KSHV has only been completed using isolates from Western countries-where KS is not endemic. The lack of whole-genome KSHV sequence data from the most clinically important geographical region, sub-Saharan Africa, represents an important gap since it remains unclear whether genomic diversity has a role on KSHV pathogenesis. We hypothesized that distinct KSHV genotypes might be present in sub-Saharan Africa compared to Western countries. Using a KSHV-targeted enrichment protocol followed by Illumina deep-sequencing, we generated and analyzed 16 unique Zambian, KS-derived, KSHV genomes. We enriched KSHV DNA over cellular DNA 1,851 to 18,235-fold. Enrichment provided coverage levels up to 24,740-fold; therefore, supporting highly confident polymorphism analysis. Multiple alignment of the 16 newly sequenced KSHV genomes showed low level variability across the entire central conserved region. This variability resulted in distinct phylogenetic clustering between Zambian KSHV genomic sequences and those derived from Western countries. Importantly, the phylogenetic segregation of Zambian from Western sequences occurred irrespective of inclusion of the highly variable genes K1 and K15. We also show that four genes within the more conserved region of the KSHV genome contained polymorphisms that partially, but not fully, contributed to the unique Zambian KSHV whole-genome phylogenetic structure. Taken together, our data suggest that the whole KSHV genome should be taken into consideration for accurate viral characterization.",
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