Details

Autor(en) / Beteiligte

• Akram, K M
• Moyo, N A
• Leeming, G H
• Bingle, L
• Jasim, S
• Hussain, S
• Schorlemmer, A
• Kipar, A
• Digard, P
• Tripp, R A
• Shohet, R V
• Bingle, C D
• Stewart, J P

Titel

An innate defense peptide BPIFA1/SPLUNC1 restricts influenza A virus infection

Ist Teil von

• Mucosal immunology, 2018-01, Vol.11 (1), p.71-81

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2018

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.