Figure 5.

Improved clinical score, viral clearance, and survival are observed with lineage-restricted MND4T vector expressing perforin. (a) Mice challenged with LCMV 16 weeks after transplantation were clinically scored three times weekly for 50 days. Clinical scoring is represented for groups until they had ≥10% survival per group (n = 10 experiments; TxWT, n = 20; MND4T, n = 35; PRF0T, n = 11; PGK4T, n = 29; TxPrf1^−/−, n = 12 mice). Error bars represent the SEM. (b) Kaplan–Meier survival curves for the same group of mice as in (a), measured up to 50 days. Statistics were done by Mantel–Cox test. (c) Length of survival (in days) among the mice with low chimerism (<60%) versus those with high chimerism (60–100%) within each group after LCMV challenge. Each symbol represents one mouse; the number of mice per group is stated above the group. Percent chimerism is derived from tNGFR-expressing NK cells at 12 weeks posttransplantation. Medians are denoted by a horizontal line. Statistics: Unpaired t test with Welch correction within each vector group. (d) LCMV mRNA in the bone marrow of mice that were either alive on day 50 (mice represented in the rectangular shaded box) or were sacrificed when moribund. mRNA expression was normalized to expression in Prf1^−/− mice sacrificed 8 days after LCMV challenge (n = 3 experiments). Medians are denoted by a horizontal line. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. ^†Death of all mice in that group.