Summary auto-generated
This study investigated the pathogenesis of pneumonia virus of mice (PVM) and human respiratory syncytial virus (HRSV) in BALB/c mice using in situ hybridization to detect viral mRNA in lung tissue sections. Following intranasal inoculation with 120 plaque-forming units (p.f.u.) of PVM, viral RNA was initially detected within 2 days in alveolar cells. As infection progressed, hybridizing cells increased in number and extended to terminal bronchioles. By days 4-5, morphological lung abnormalities appeared that correlated with clinical signs of respiratory distress. Virus was cleared below detection levels by day 10 post-infection in surviving mice. Mice infected with 1500 p.f.u. HRSV showed markedly different viral RNA distribution, predominantly in peribronchiolar and perivascular regions by day 5, with PVM producing considerably higher viral yields than HRSV. The distinct distribution patterns between these two pneumoviruses suggest they have different tissue tropism in the mouse lung and may explain differences in disease severity and the limited utility of mice as models for human HRSV infection.
Key findings
- PVM viral mRNA was detected as early as day 2 post-infection, initially in alveolar cells and progressing to terminal bronchioles with morphological lung damage peaking at days 4-5 coinciding with severe clinical signs
- PVM reached peak lung titers of 6.7×10⁵ p.f.u./g on day 5 post-infection and viral RNA was cleared below detection levels by day 10, with all surviving mice appearing healthy after day 12
- HRSV and PVM showed distinctly different distribution patterns in infected mouse lungs, with HRSV predominantly localized to peribronchiolar and perivascular regions versus widespread alveolar and bronchiolar infection with PVM
- PVM produced significantly higher viral yields from mouse lungs compared to HRSV, despite similar infection timescales
- The restricted tropism of HRSV in mice compared to its widespread distribution in naturally infected humans suggests the mouse model may have limited utility for studying human HRSV pathogenesis
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Abstract
The pathogenesis of pneumonia virus of mice (PVM) and human respiratory syncytial virus (HRSV) in BALB/c mice were investigated by using in situ hybridization to detect virus mRNA in fixed lung sections. Following intranasal inoculation with 120 p.f.u. PVM the pattern of hybridization showed that virus mRNA was initially detected within 2 days in alveolar cells. As the infection progressed the number of hybridizing alveolar cells increased and signal was also detected in cells lining the terminal bronchioles. By days 4 to 5 post-infection areas of morphological abnormality could be seen, particularly in the strongly hybridizing regions of the lung, and this correlated with the appearance of clinical signs of infection. In animals which survived the infection virus-specific mRNA could not be detected 10 days post- infection. Mice infected with 1500 p.f.u. HRSV showed significant differences in the distribution of virus-specific mRNA when compared to the pattern seen with PVM. HRSV mRNA was detected over large areas, but predominantly in peribronchiolar and perivascular regions of the lungs 5 days post-infection. The yield of PVM from infected mouse lungs was considerably higher than that of HRSV. The possible implications of these results for the use of the mouse model for pneumovirus infections are discussed.