tetano
Editor, Senior Moderator
Mucosal Immunol. 2017 May 17. doi: 10.1038/mi.2017.45. [Epub ahead of print]
[h=1]An innate defense peptide BPIFA1/SPLUNC1 restricts influenza A virus infection.[/h] Akram KM[SUP]1[/SUP], Moyo NA[SUP]2[/SUP], Leeming GH[SUP]2,[/SUP][SUP]3[/SUP], Bingle L[SUP]4[/SUP], Jasim S[SUP]5[/SUP], Hussain S[SUP]5[/SUP], Schorlemmer A[SUP]6[/SUP], Kipar A[SUP]2,[/SUP][SUP]3,[/SUP][SUP]7[/SUP], Digard P[SUP]5[/SUP], Tripp RA[SUP]8[/SUP], Shohet RV[SUP]6[/SUP], Bingle CD[SUP]1[/SUP], Stewart JP[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The airway epithelium secretes proteins that function in innate defense against infection. Bactericidal/permeability-increasing fold-containing family member A1 (BPIFA1) is secreted into airways and has a protective role during bacterial infections, but it is not known whether it also has an antiviral role. To determine a role in host defense against influenza A virus (IAV) infection and to find the underlying defense mechanism, we developed transgenic mouse models that are deficient in BPIFA1 and used these, in combination with in vitro three-dimensional mouse tracheal epithelial cell (mTEC) cultures, to investigate its antiviral properties. We show that BPIFA1 has a significant role in mucosal defense against IAV infection. BPIFA1 secretion was highly modulated after IAV infection. Mice deficient in BPIFA1 lost more weight after infection, supported a higher viral load and virus reached the peripheral lung earlier, indicative of a defect in the control of infection. Further analysis using mTEC cultures showed that BPIFA1-deficient cells bound more virus particles, displayed increased nuclear import of IAV ribonucleoprotein complexes, and supported higher levels of viral replication. Our results identify a critical role of BPIFA1 in the initial phase of infection by inhibiting the binding and entry of IAV into airway epithelial cells.Mucosal Immunology advance online publication 17 May 2017; doi:10.1038/mi.2017.45.
PMID: 28513596 DOI: 10.1038/mi.2017.45
[h=1]An innate defense peptide BPIFA1/SPLUNC1 restricts influenza A virus infection.[/h] Akram KM[SUP]1[/SUP], Moyo NA[SUP]2[/SUP], Leeming GH[SUP]2,[/SUP][SUP]3[/SUP], Bingle L[SUP]4[/SUP], Jasim S[SUP]5[/SUP], Hussain S[SUP]5[/SUP], Schorlemmer A[SUP]6[/SUP], Kipar A[SUP]2,[/SUP][SUP]3,[/SUP][SUP]7[/SUP], Digard P[SUP]5[/SUP], Tripp RA[SUP]8[/SUP], Shohet RV[SUP]6[/SUP], Bingle CD[SUP]1[/SUP], Stewart JP[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The airway epithelium secretes proteins that function in innate defense against infection. Bactericidal/permeability-increasing fold-containing family member A1 (BPIFA1) is secreted into airways and has a protective role during bacterial infections, but it is not known whether it also has an antiviral role. To determine a role in host defense against influenza A virus (IAV) infection and to find the underlying defense mechanism, we developed transgenic mouse models that are deficient in BPIFA1 and used these, in combination with in vitro three-dimensional mouse tracheal epithelial cell (mTEC) cultures, to investigate its antiviral properties. We show that BPIFA1 has a significant role in mucosal defense against IAV infection. BPIFA1 secretion was highly modulated after IAV infection. Mice deficient in BPIFA1 lost more weight after infection, supported a higher viral load and virus reached the peripheral lung earlier, indicative of a defect in the control of infection. Further analysis using mTEC cultures showed that BPIFA1-deficient cells bound more virus particles, displayed increased nuclear import of IAV ribonucleoprotein complexes, and supported higher levels of viral replication. Our results identify a critical role of BPIFA1 in the initial phase of infection by inhibiting the binding and entry of IAV into airway epithelial cells.Mucosal Immunology advance online publication 17 May 2017; doi:10.1038/mi.2017.45.
PMID: 28513596 DOI: 10.1038/mi.2017.45