Abstract
Influenza virus infection results in a respiratory disease that ranges in severity from sub-clinical infection to primary viral pneumonia. We investigated the effect of inoculation of amantadine sensitive A/Puerto Rico/8/1934 (H1N1) [PR8] in mice and evaluated the viral pathogenicity and pulmonary inflammation over a 7 day time course.
Balb/c mice were infected intranasally with vehicle or H1N1 (4, 40 or 400 PFU) on one occasion. Cellular influx and cytokine levels were assessed in BAL and viral load measured in lung lysate on Days 1, 3, 5 and 7.
A dose dependent increase in lung viral titre peaked on Day 3-5 post inoculation coinciding with peak inflammatory cell infiltrate. Maximal recruitment of neutrophils 0.85 vs 0.02 x 106/animal in PBS control group) and lymphocytes (0.14 vs 0.003 x 106/animal in PBS control group) was recorded on Day 5. BAL cytokines (including IP-10 and KC) were elevated as early as 24 h following inoculation. TNF-α and KC peaked on Day 3 and remained significantly higher than the PBS control group out to Day 7. A significant increase in Penh was recorded on Day 3 (308% and 533% increase vs PBS control, 40 and 400 PFU respectively). A dose and time dependent decrease in bodyweight was recorded from Day 3 at 400 PFU (6.9%), peaking at Day 6 (22.7%). Increase in severity of viral induced histopathology including hyaline–like membrane formation was observed with increasing PFU concentration and time.
We have demonstrated that inoculation with H1N1 (PR8) influenza virus initiates a time and dose dependent viral replication within lung tissue, resulting in cellular influx, histopathological changes and alteration in lung function.
- © 2014 ERS
