Local production of CCL3, CCL11, and IFN-γ correlates with disease severity in murine parainfluenza virus infection.

BACKGROUND

Using a murine model of parainfluenza virus infection (mPIV1 or Sendai virus; SeV), we compared the inflammatory responses to lethal and sub-lethal infections in inbred DBA/2 mice.

METHODS

Mice were intranasally inoculated with either 1.6×10(3) or 1.6×10(5) infectious units (IU) 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 9-14. Clarified whole lung homogenates were evaluated for inflammatory markers by enzyme-linked immunoassay (ELISA). Data were analyzed using ANOVA or Student t-tests, as appropriate.

RESULTS

Mice inoculated with 1.6×10(5) IU of SeV developed a lethal infection with 100% mortality by day 7, while mice inoculated with 1.6×10(3) IU developed a clinically significant infection, with universal weight loss but only 32% mortality. Interestingly, peak virus recovery from the lungs of mice inoculated with 1.6×10(5) IU of SeV did not differ substantially from that detected in mice that received the 100-fold lower inoculum. In contrast, concentrations of CCL5 (RANTES), CCL11 (eotaxin), interferon-γ, CXCL10 (IP-10), and CCL3 (MIP-1α) were significantly higher in lung tissue homogenates from mice inoculated with 1.6×105 IU (p < 0.05). In the lethal infection, levels of CCL11, interferon- γ and CCL3 all correlated strongly with disease severity.

CONCLUSION

We observed that severity of SeV-infection in DBA/2 mice was not associated with virus recovery but rather with the levels of proinflammatory cytokines, specifically CCL11, interferon- γ and CCL3, detected in lung tissue in response to SeV infection.