Fig. 1: KSHV infection elicits an expansion of CD8⁺ T cells in EBV co-infected humanized mice.

A Experimental outline of EBV and KSHV infections in NSG mice reconstituted with human fetal liver derived CD34⁺ HPCs. Animals were infected intraperitoneally (i.p.) with KSHV and/or wild-type EBV (EBVwt), lytic replication deficient BZLF-1 knock-out EBV (EBVzko) or mock-infected with PBS at the age of three to six months and euthanized at 4 weeks post infection (p.i.) or when predetermined euthanasia criteria were met. B Co-staining of LANA with CD20, CD3 and CD68 on splenic sections of EBVwt (left) and EBVwt+KSHV (right) infected mice. C Human CD45⁺CD3⁺CD8⁺, CD45⁺CD3⁺CD4⁺ and CD45⁺CD19⁺ cells/ml blood measured before infection (baseline, BL) and at experiment termination (end point, EP). Composite data from 13 independent experiments for T cell data with N = 35 (mock), N = 24 (EBVzko), N = 28 (KSHV+EBVzko), N = 26 (EBVwt) and N = 22 (KSHV+EBVzko) mice; and from 12 independent experiments for B cell data with N = 36 (mock), N = 24 (EBVzko), N = 29 (KSHV+EBVzko), N = 28 (EBVwt) and N = 17 (KSHV+EBVwt) mice. Two sided Wilcoxon test. Significant p-values left to right: CD8: 0.04383; 5.329e-5; 5.53e-5; 0.0003636; 0.0006938; B cells: 6.657e-6; 0.002815; 1.193e-5; 5.245e-6; 3.052e-5. D Number of human CD45⁺CD3⁺CD8⁺, CD45⁺CD3⁺CD4⁺ and CD45⁺CD19⁺ cells per spleen. Composite data from 14 independent experiments for T cells with N = 34 (CD8) and 38 (CD4) (mock), N = 32 (CD8) and 21 (CD4) (EBVzko), N = 19 (KSHV+EBVzko), N = 36 (EBVwt), N = 30 (KSHV+EBVwt) mice, and 10 independent experiments for B cells with N = 28 (mock), N = 18 (EBVzko), N = 16 (KSHV+EBVzko), N = 27 (EBVwt) and N = 15 (KSHV+EBVwt) mice. Kruskal Wallis followed by Dunn’s test with Bonferroni (BF)-corrected p-values. Significant p values from left to right: CD8: 4.761e-3; 3.5799e-5; 6.577e-6; 2.116e-10; CD4: 0.006. E CD45⁺CD3⁺CD8⁺ and CD45⁺CD3⁺CD4⁺ cell numbers measured at 4 weeks p.i. in the blood or (F) spleen, normalized to the respective EBVzko or EBVwt single-infected group per experiment. Composite data of (E) 7 (EBVzko) and 8 (EBVwt) independent experiments with N = 26 (Ezko), N = 29 (KSHV+Ezko), N = 27 (Ewt), N = 24 (KSHV+Ewt). Two sided Mann Whitney U Test (MWU), significant p-values from left to right: 0.01297  (F) 6 (EBVzko) and 11 (EBVwt) independent experiments with N = 21 (Ezko), N = 20 (KSHV+Ezko), N = 36 (Ewt), N = 30 (KSHV+Ewt). Two sided MWU, significant p values from left to right: 0.008417; 0.03508. *p < 0.05, **p < 0.01, ***p < 0.001. D–F Box plot hinges correspond to 25^th and 75^th percentiles, shown are median and Turkey Whiskers. Source data are provided as a Source data file.