Figure 1. Progression of CIA in latent γHV68-infected and control uninfected mice.

(A) Clinical score (y-axis) of collagen-induced arthritis (CIA) measured three times weekly for 8 weeks (x-axis; days) post-CIA induction in mice without (CIA, filled circles) and with latent γHV68 infection (γHV68-CIA, open squares), and starting at day 35 post-infection in mice infected with latent γHV68 infection but not induced for CIA (γHV68, filled triangles). (B) Change (Δ, y-axis) in thickness of hind paws measured with calipers once per week and averaged for each mouse, γHV68-CIA and CIA being measured on the day of CIA induction and γHV68 at day 35 post-infection. (C) Day (y-axis) of CIA onset (considered 2 consecutive scoring days of a score of at least 1) in mice (x-axis) without (CIA) and with latent γHV68 infection (γHV68-CIA). Each data point represents an individual mouse. (A–C) Data presented as mean ± SEM. Statistical significance determined by (A, B) two-way ANOVA with multiple comparisons with F-values 329.22 (A) and 17.95 (B), (C) Mann-Whitney test. ****p<0.0001, ***p<0.001, **p<0.01, *p<0.05. (A) n = 10–29 mice per group, four experiments; (B) n = 8–20 mice per group, three experiments; (C) n = 26–29 mice per group, four experiments.

Figure 1—figure supplement 1. Clinical data, autoantibody titers, and viral load.

(A) Representative photographs of paws with a corresponding collagen-induced arthritis (CIA) clinical score of 1, 2, and 3. (B) Area under the curve, same clinical data as in Figure 1A, each data point representing the total area under the curve for an individual mouse, (C) clinical score per mouse at day 56 post-CIA induction for CIA and γHV68-CIA mice, (D) sum of clinical scores for each individual mouse during the observation period, (E) clinical scores (y-axis) over the course of CIA (x-axis, days post-induction) in mice (n = 11–17 mice per group, same data as in Figure 1A) without (CIA) and with (γHV68-CIA) latent γHV68 infection, separated by sex. (F–H) Optical density (OD, y-axis) reflecting titers (x-axis; dilution of serum) of anti-type II collagen antibodies separated by (F) total IgG, (G) IgG1, and (H) IgG2c in naive (black circles), CIA (gray circles), and γHV68-CIA (open squares) mice; n = 3–4 mice per group. (I) Viral load in the spleen of γHV68 (day 35 p.i.) and γHV68-CIA (56 days post-CIA induction) mice, determined by quantitative PCR (qPCR). Data presented as mean ± SEM. Data presented as mean ± SEM and analyzed by (B, I) Mann-Whitney test, (C–D) one-way ANOVA, and (E) two-way ANOVA with multiple comparisons; *p<0.01, *p<0.05.