Ythdf2-deficient NK cells have impaired antiviral functions. (A) 2.5 × 10⁴ PFU MCMV were injected i.p. into Ythdf2^WT and Ythdf2^ΔNK mice. Weight loss of Ythdf2^WT and Ythdf2^ΔNK mice at various times after infection is shown, presented as relative weights compared with before infection (n = 5 mice for MCMV groups, and n = 3 for PBS groups). (B) Viral titers in peripheral blood mononuclear cells on day 7 after infection were assessed by qPCR. Mice injected with PBS were used as control (n = 5 mice for MCMV groups; n = 3 for PBS groups). (C and D) The percentage and absolute number of NK cells in the spleen from Ythdf2^WT and Ythdf2^ΔNK mice on days 0, 4, 7 after infection with MCMV (n = 3 at days 0 and 4; n = 5 at day 7). (E–G) Representative plots (E) and quantification of Ki67 expression by NK cells in the spleen (F) and blood (G) from Ythdf2^WT and Ythdf2^ΔNK mice on day 7 after infection (n = 5 mice per group). (H–J) Representative plots (H) and quantification of the percentage (I) and absolute number (J) of Ly49H⁺ NK cells in spleen from Ythdf2^WT and Ythdf2^ΔNK mice on days 0, 4, 7 after infection with MCMV (n = 3 at days 0 and 4; n = 5 at day 7). (K–M) Representative plots (K) and quantification of perforin expression by NK cells in the spleen (L) and blood (M) from Ythdf2^WT and Ythdf2^ΔNK mice on day 7 after infection (n = 5 mice per group). Data are shown as mean ± SD and were analyzed by unpaired two-tailed t test (F, G, L, and M), one-way ANOVA with Šídák post-test (B), or two-way ANOVA with Šídák post-test (A, C, D, I, and J). Data are representative of at least three independent experiments. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001.