1726. Pulmonary Inflammatory Responses to Sendai Virus Infection in Susceptible and Resistant Mouse Strains
Session: Poster Abstract Session: Studies of the Interface of Host-Microbial Interaction
Saturday, October 5, 2013
Room: The Moscone Center: Poster Hall C
Background: Using a murine model of parainfluenza virus (Sendai;SeV) lower respiratory tract infection, we compared the inflammatory responses to infection in susceptible and resistant mouse strains.

Methods: DBA/2 and C57BL/6 mice were inoculated intranasally with ~1.6x103 or ~1.6x105 infectious particles of SeV, or diluent control. Clinical data including daily weights, oxygen saturation, and lung function, via whole body plethysmography were collected on days 0, 3-7, and 10-14. Lungs were assayed for inflammatory markers by gene microarray and enzyme-linked immunoassay.

Results: SeV infected C57BL/6 mice developed a clinical infection similar to DBA/2 mice receiving 100-fold less virus. Peak virus titers were 7.7x107/105 copies GADPH on day 5 for both mouse strains. However, despite receiving a 100-fold higher inoculum, C57BL/6 mice were able to clear the virus by day 14, while the lung virus titers in the DBA/2 mice remained elevated (2.2x104/105 copies GAPDH). Despite similar clinical symptoms, 15/16 (90%) of the SeV infected C57BL/6 mice survived the 14-day observation period, while only 10/16 (63%) of the DBA/2 mice survived. DBA/2 mice that received the higher inoculum had similar lung function, oxygen saturation, and virus titers when compared to the other groups, but they sustained significantly more weight loss, and mortality was 100% by day 7 of infection. These mice produced earlier and higher lung concentrations of interferon- γ, CCL3, CCL5, and CCL11 than the other 2 groups (p<0.05).  Infected C57BL/6 mice produced earlier and higher concentrations of CCL3, CCL5, CCL11, and interferon-γ than DBA/2 mice infected with 100-fold lower inoculum, but not as high as those produced by DBA/2 mice with lethal infection. CCL3 was the only chemokine that correlated with weight loss in all three groups.

Conclusion: Strain-specific inflammatory responses to SeV infection result in differences in virus clearance, lung inflammation, and mortality between susceptible and resistant mouse strains.

Manika Suryadevara, MD, Cynthia Bonville, MS and Joseph Domachowske, MD, SUNY Upstate Medical University, Syracuse, NY

Disclosures:

M. Suryadevara, None

C. Bonville, None

J. Domachowske, Sanofi Pasteur: Consultant, Consulting fee, Research grant, Research support and Speaker honorarium
GlaxoSmith Kline: Consultant, Consulting fee, Research grant, Research support and Speaker honorarium
Medimmune: Consultant, Consulting fee and Speaker honorarium
Pfizer: Grant Investigator, Research grant and Research support
Novartis: Consultant, Consulting fee, Research support and Speaker honorarium
Merck: Consultant, Consulting fee and Speaker honorarium

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