Fig. 1

Aged mice had more severe HMPV disease and delayed viral clearance. A Aged infected mice lost more weight during HMPV infection, P < 0.0001 days 4–9 p.i. for aged vs. young HMPV. B Aged mice had more severe clinical signs throughout infection. Clinical signs included: hunched, rapid breathing, lethargy, and ruffled fur with one point given for each sign observed. Two individuals independently scored each mouse daily and average score was calculated, P < 0.0001 on day 2–9 p.i. for aged vs. young HMPV. C Aged mice had delayed HMPV clearance. Viral titer in lung in PFU/g was quantified using plaque assay and normalized to lung weight. Dotted line indicates limit of detection (LOD). D Aged infected mice accumulated more inflammatory infiltrates in the perivascular and peribronchial spaces in the lung by day 9 p.i. The histopathology score: average score per section field by a group-blinded experienced lung pathologist. 0 = no inflammation, 1 =  < 25% inflammation, 2 = 25–50% inflammation, 3 = 50–75% inflammation, and 4 =  > 75% inflammation. E & F Representative lung histology at day 9 p.i. G Aged and young TN/94–49 HMPV infected mice were treated with either αCD8 blocking antibody (Ab) or rat isotype control Ab. Aged vs. young isotype groups weight loss significant at days 3, 4, 8, and 9 p.i; aged vs. young αCD8 groups significant at days 4, 5, 8, and 9 p.i. H Aged αCD8 mice tended to have delayed viral clearance compared to young αCD8 mice. Dotted line indicates LOD. Number of mice per group at D5, D7, and D9, respectively: Aged isotype (n = 3,7,6), Young isotype (n = 3,7,6), Aged αCD8 (n = 3, 9, 7), Young αCD8 (n = 3,8,7). Number of mice per group below LOD at D5, D7, and D9, respectively: Aged isotype (n = 0/3,0/7,4/6), Young isotype (n = 0/3,7/7,6/6), Aged αCD8 (n = 0/3,0/9,4/7), Young αCD8 (n = 0/3,6/8,7/7). *P < 0.05,**P < 0.01, ***P < 0.001, # = ****P < 0.0001, one or two-way ANOVA