(A) Splenic endpoint viral DNA load and (B) viral DNA load per gram lymph node tissue determined by qPCR of huNSG mice infected with either 105 RIU of wt, 3AKO or 3CKO for 5 weeks (spleen: n = 18-21/group, lymph node: n = 8-11/group) or 106 RIU of 3AKO or 3CKO for 6 weeks (spleen: n = 13-14/group, lymph node: n = 12-13/group). Values for mice in which no viral DNA was detected are plotted on the X-axis. (C) Blood DNA viral load over time determined by qPCR of huNSG mice infected with either 105 RIU of wt, 3AKO or 3CKO 5 weeks p.i. (n = 18-21/group) or 106 RIU of 3AKO or 3CKO 6 weeks p.i. (n = 13-14/group). Horizontal dashed line indicates the viral load of 3 times the lower limit of quantification (LLOQ). Horizontal dotted line indicates the LLOQ. (D) Frequency of huNSG mice infected with 105 RIU of 3AKO, 3CKO or wt 5 weeks p.i. or 106 RIU of 3AKO or 3CKO 6 weeks p.i. with EBV DNA copies above (≥200) or below (<200) 3 times the LLOQ in either the blood, the spleen or lymph nodes (n = 10-13/group) as determined by qPCR. Pooled data from 4 low and 2 high infectious dose experiments. *P < 0.05, **P < 0.01, Fisher’s exact test. (E) EBER-ISH (original magnification, 400x) of splenic sections from huNSG mice infected with 106 RIU of 3AKO or 3CKO 6 weeks p.i.. (G) EBER-ISH (original magnification, 200x) of splenic sections from huNSG mice infected with 105 RIU of 3AKO or 3CKO 12 weeks p.i.. (F, H) Quantification of EBER+ cells/mm2 of E (n = 10-13/group) and G (n = 3-5/group) respectively and of huNSG mice infected with 105 RIU of wt 5 weeks p.i. (n = 4/group) or mock (n = 3-8/group). (I) Frequency of huNSG mice infected with 105 RIU of 3AKO or 3CKO 12 weeks p.i., with EBV DNA copies above (≥200) or below (<200) 3 times the LLOQ in either the blood, the spleen or lymph nodes (n = 3-5/group) as determined by qPCR. Pooled data from 2 experiments. (A-C) Pooled data from 4 low and 2 high infectious dose experiments are displayed with mean ± SEM. **P < 0.01, ***P < 0.001, two-way ANOVA with Bonferroni correction for blood viral load and Mann-Whitney U test for splenic viral load, lymph node viral load and EBER-ISH.