Fig 2: KSHV infection drives CD56-CD16+ NK cell differentiation with expression of CD38, CD39, CD69, and CXCR6 in huNSG mice(A) UMAP visualization of single, live, human CD45+Lin- (CD3, CD19, CD14, CD4) CD7+ cells isolated at 4 weeks p.i. from spleen and liver of mock-, EBVzko-, and EBVzko+KSHV-infected mice depicted as contour plot.(B) UMAP plot depicting relative marker expression from samples in (A). (C) Heatmap depicting median fluorescent intensity (MFI) of surface markers on CD56-and CD16-stained NK cell subsets (pre-gated on human CD45+NKp46+Lin-) and on human CD45- cells of EBVzko+KSHV co-infected animals.(D) Heatmap depicting the median frequency of cells positive for indicated surface markers among different CD56-and CD16-stained NK cell subsets. In (C) and here, composite data are from 1–4 independent experiments with n = 6–20 animals. Data are normalized per column. Statistical analysis was performed by multiple comparison tests following paired one-way ANOVA or Friedmann’s test (q values). See also Figures S3A and S3B.(E and F) Expression of (E) CD38 and CD2 or (F) CXCR6 and CD62L among splenic and hepatic NK cells. Colors in the pie charts indicate CD56/CD16 subsets. Pie arc colors depict the expression of (E) CD38 and CD2 or (F) CXCR6 and CD62L. In (E), scatterplots depict subset frequencies within NKp46+ cells of individual mice (symbol color: black, spleen; clear, liver). Median.(G) Frequencies of CXCR6+ splenic or hepatic NK cells.(H and I) Frequencies of cells expressing (H) CD69 or (I) CD39 among CXCR6+ and CXCR6- NK cells from EBVzko+KSHV mice. Wilcoxon test.In (G)–(I), three independent experiments. Median (IQR). In (C)–(I), NK cells were pre-gated on huCD45+, live, Lin- (CD3, CD19, CD14, CD4) NKp46+ cells. *p < 0.05, **p < 0.01, ***p < 0.001. Unless otherwise stated, statistical analysis was performed by Dunn’s test following KW test (q values).See also Figures S2 and S3.