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

Antiviral Res. 2012 Nov;96(2):158-68. doi: 10.1016/j.antiviral.2012.08.012. Epub 2012 Sep 6.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / cytology
  • Chemokines / biosynthesis
  • Coronavirus Infections / immunology
  • Coronavirus Infections / virology
  • Disease Models, Animal
  • Gene Expression Profiling
  • Lung / immunology
  • Lung / virology
  • Lymph Nodes / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Murine hepatitis virus / immunology*
  • Neutrophils / immunology*
  • Proteins / immunology
  • Proteins / metabolism*

Substances

  • Chemokines
  • Proteins
  • Wfdc1 protein, mouse