Figure 3.

RV-1B replication and induction of innate (antiviral IFN) and acquired virus-specific cellular and humoral immune responses in BALB/c mice. Groups of four mice were inoculated with 5 × 10⁶ TCID₅₀ of RV-1B or UV–RV-1B. (a) Quantification of rhinovirus RNA in lung homogenates by quantitative RT-PCR. (b) Quantification of rhinovirus viral load in total BAL, as measured by titration of infectious virus in HeLa cells. (c) In situ hybridization staining of lung sections from mice infected with RV-1B, RV-16 or UV–RV-1B. Top row, sections probed with antisense RNA probe to detect genomic viral RNA. Bottom row, sections probed with sense RNA probe to detect negative-strand replicative viral RNA. Sections probed with a respiratory syncytial virus M protein–specific probe³⁰ were negative (data not shown). Sections are representative of three mice per group. (d) Induction of antiviral IFNs α, β and λ in BAL, as measured by quantitative ELISA. (e) Frequency of IFN-γ–producing lung leukocytes in mice infected with RV-1B assessed at day 4 (left) or day 7 (right) after infection, cultured with or without RV-1B stimulation ex vivo. ^###P < 0.001 comparing mice dosed with RV-1B to mice dosed with RV-16. At day 7, induction was virus-specific, ⁺⁺⁺P < 0.001 for leukocytes stimulated ex vivo with RV-1B compared to unstimulated cells. (f) Rhinovirus-specific IgG measured by ELISA in serum collected at the indicated day after infection. All data are expressed as means ± s.e.m., *P < 0.05, **P < 0.01 and ***P < 0.001 for RV-1B compared with UV-inactivated control.