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. 2008 Jun;42(2):165-71.
doi: 10.1016/j.jcv.2008.02.006. Epub 2008 Apr 3.

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

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

Tiffany White et al. J Clin Virol. 2008 Jun.

Abstract

Background: Kaposi's sarcoma-associated herpesvirus (KSHV) encodes genetically diverse K1 alleles which have unique geographic distributions. Little is known about K1 genetic diversity in Zimbabwe where acquired immunodeficiency syndrome-associated KS (AIDS-KS) is epidemic.

Objective: Evaluate K1 diversity in Zimbabwe and compare Zimbabwean K1 diversity to other areas in Africa.

Study design: K1 nucleotide sequence was determined for AIDS-KS cases in Zimbabwe. K1 references sequences were obtained from Genbank.

Results: Among 65 Zimbabwean AIDS-KS cases, 26 (40%) were K1 subtype A and 39 (60%) were subtype B. Zimbabwean subtype A sequences grouped only with African intratype A5 variants. Zimbabwean subtype B sequences grouped with multiple intratype African variants: 26 B1 (26%), four B3 (6%) and nine highly divergent B4 (14%). Zimbabwean subtype B had a lower synonymous to nonsynonymous mutation ratio (median 0.59 versus 0.66; P=0.008) and greater distance to the most recent common ancestor (median 0.03 versus 0.009; P<0.001) compared to subtype A. Within the B subgroup, the distribution of intratype B variants differed in Zimbabwe and Uganda (P=0.004).

Conclusions: Greater positive selection and genetic diversity in K1 subtype B compared to subtype A5 exist in Zimbabwe. However, there were no significant associations between K1 subtype and the clinical or demographic characteristics of AIDS-KS cases.

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Figures

Figure 1
Figure 1
Phylogenetic analysis of Kaposi’s sarcoma associated herpesvirus (KSHV) K1 in Zimbabwe. The inferred tree includes DNA sequences amplified from plasma or peripheral blood mononuclear cell samples from 65 Zimbabwean subjects and 60 reference sequences from previous studies. The BC-2 sequence was used as the out-group for depiction of the tree. Bootstrap values calculated from 1000 replicate trees are noted at major branch points as a percentage. Horizontal branch lengths are drawn to scale, with the bar at the bottom left corner representing 10% divergence. Letters after patient identifiers: C, peripheral blood mononuclear cell; P, plasma. Letters within reference identifiers: G, The Gambia, SA, South Africa; Tanz, Tanzinia; Ugd, Uganda; Zam, Zambia; Zim, Zimbabwe. Arrows indicate the most recent Zimbabwean common ancestor (MRCA) node for the A5 and B groups. Subgroup classification is as proposed by Kajumbula, et al., except for the designation of new B4 subgroup that was supported by a bootstrap value of 98%.
Figure 2
Figure 2
Phylogenetic analysis of Kaposi’s sarcoma associated herpesvirus (KSHV) K1 subgroup A5, B1 and B2 protein sequences inferred from the DNA sequences in Figure 1. The BC-2 sequence was used as the out-group for depiction of the tree. Horizontal branch lengths are drawn to scale, with the bar at the bottom left corner representing 10% divergence. Letters after patient identifiers: C, peripheral blood mononuclear cell; P, plasma. Letters within reference identifiers: G, The Gambia; SA, South Africa; Tanz, Tanzania; Ugd, Uganda; Zam, Zambia; Zim, Zimbabwe. Subgroup classification is the same as in Figure 1.
Figure 3
Figure 3
Per codon nonsynonymous and synonymous mutation rates and synonymous to nonsynonymous mutation ratio (dS/dN) for the VR1-VR2 region of Zimbabwean K1 genes. (A) Zimbabwean subtype A5 K1 nucleotide sequences from Figure 1; (B) Zimbabwean subtype B K1 nucleotide sequences from Figure 1. The location of the K1 hypervariable regions (VR1 and VR2) is indicated by bars at the bottom.
Figure 4
Figure 4
K1 nucleotide sequence distance to the most common recent Zimbabwean ancestor (MRCA). Each point represents the nucleotide sequence difference between a Zimbabwean K1 DNA sequence and the MRCA for Zimbabwean sequences within the A and B subtypes shown by the arrows in Figure 1. Horizontal bars are the median distance for each grouping from the Zimbabwe MRCA for either the A or B subtypes.

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