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 high CD62L 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.