Increased Constitutive Interferon-β Levels and Altered CD4 T Cell Homeostasis Induced by Expression of a Viral Glycoprotein

Abstract

Besides the strong Type I interferon (IFN-I) response induced by infections, IFN-I is also produced constitutively at lower levels. Constitutive IFN-I production is regulated by resident microbiota and is essential for induction of efficient immune responses. Here, we demonstrate in transgenic (tg) mice that expression of a single viral envelope gene, the glycoprotein (GP) of lymphocytic choriomeningitis virus (LCMV), increased constitutive IFN-β levels and induced numerous IFN-stimulated genes (ISGs). In addition, self-antigen-driven CD44^highCD62L^low memory-phenotype CD4 T cells and regulatory CD4 T cell populations were enlarged in these LCMV GP-tg mice; by contrast, the fraction of bona fide antigen-specific memory CD4 T cells remained unchanged. Our study demonstrates that expression of a single viral envelope gene increased constitutive IFN-β levels, induced upregulation of ISGs, and altered CD4 T cell homeostasis. Our results further suggest that a hitherto undefined signaling pathway capable of inducing IFN-β expression can detect LCMV GP at the protein or transcript level.