title: WFDC1/ps20: a host factor that influences the neutrophil response to murine hepatitis virus (MHV) 1 infection.
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.
authors.affiliation: Toronto General Research Institute, Division of Cell and Molecular Biology, University Health Network, 67 College Street, Toronto, Ontario, Canada M5G 2M1.
authors.forename: Erin
authors.initials: E
authors.lastname: Rogers
authors.forename: Ben X
authors.initials: BX
authors.lastname: Wang
authors.forename: Zhu
authors.initials: Z
authors.lastname: Cui
authors.forename: David R
authors.initials: DR
authors.lastname: Rowley
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Ressler
authors.forename: Annapurna
authors.initials: A
authors.lastname: Vyakarnam
authors.forename: Eleanor N
authors.initials: EN
authors.lastname: Fish
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018925:Chemokines / Q000096:biosynthesis; D018352:Coronavirus Infections / Q000276:immunology / Q000821:virology; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D008168:Lung / Q000276:immunology / Q000821:virology; D008198:Lymph Nodes / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D006517:Murine hepatitis virus / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D011506:Proteins / Q000276:immunology / Q000378:metabolism*
chemical_list: D018925:Chemokines; D011506:Proteins; C484311:Wfdc1 protein, mouse