Mouse guanylate-binding protein 1 does not mediate antiviral activity against influenza virus in vitro or in vivo

Abstract

Many interferon (IFN)-stimulated genes are upregulated within host cells following infection with influenza and other viruses. While the antiviral activity of some IFN-stimulated genes, such as the IFN-inducible GTPase myxoma resistance (Mx)1 protein 1, has been well defined, less is known regarding the antiviral activities of related IFN-inducible GTPases of the guanylate-binding protein (GBP) family, particularly mouse GBPs, where mouse models can be used to assess their antiviral properties in vivo. Herein, we demonstrate that mouse GBP1 (mGBP1) was upregulated in a mouse airway epithelial cell line (LA-4 cells) following pretreatment with mouse IFNα or infection by influenza A virus (IAV). Whereas doxycycline-inducible expression of mouse Mx1 (mMx1) in LA-4 cells resulted in reduced susceptibility to IAV infection and reduced viral growth, inducible mGBP1 did not. Moreover, primary cells isolated from mGBP1-deficient mice (mGBP1^-/- ) showed no difference in susceptibility to IAV and mGBP1^-/- macrophages showed no defect in IAV-induced NLRP3 (NLR family pyrin domain containing 3) inflammasome activation. After intranasal IAV infection, mGBP1^-/- mice also showed no differences in virus replication or induction of inflammatory responses in the airways during infection. Thus, using complementary approaches such as mGBP1 overexpression, cells from mGBP1^-/- mice and intranasal infection of mGBP1^-/- we demonstrate that mGBP1 does not play a major role in modulating IAV infection in vitro or in vivo.

Keywords: GTPase; influenza A virus; innate immunity; interferon-stimulated gene.