WFDC1/ps20: A host factor that influences the neutrophil response to murine hepatitis virus (MHV) 1 infection

Rogers, Erin; Wang, Ben X.; Cui, Zhu; Rowley, David R.; Ressler, Steven J.; Vyakarnam, Annapurna; Fish, Eleanor N.

The whey acidic protein family member, WFDC1/ps20 is a permissivity factor in HIV infection. Herein we describe a contrasting role for ps20 in limiting MHV-1 infection. Intranasal MHV-1 infection produces a respiratory infection in mice. Using ps20 knockout mice we provide evidence that intranasal MHV-1 infection results in increased lung viral titers in ps20(−/−) compared to ps20(+/+) mice. Accompanying MHV-1 infection we observe an increase in the number of neutrophils infiltrating the BAL and an increase in the percentage of neutrophils in the lung draining lymph nodes of ps20(−/−) compared with ps20(+/+) mice. Gene expression levels for the neutrophil chemoattractants CXCL1 and CXCL2 are elevated in the lungs of ps20(−/−) mice post-MHV-1 infection. Characterization of the immune cell profile in naïve ps20(−/−) mice revealed an increase in circulating neutrophils compared to ps20(+/+) mice. No notable differences in other immune cell profiles were observed between the ps20(+/+) and ps20(−/−) mice. Accordingly, we examined MHV-1 infection of neutrophils and provide evidence that neutrophils isolated from ps20(−/−) mice are more susceptible to MHV-1 infection than neutrophils isolated from ps20(+/+) mice. These data suggest roles for ps20 in regulating expression of neutrophil-specific chemotactic factors, thereby potentially modulating neutrophil migration, and in modulating neutrophil susceptibility to MHV-1 infection.