Role of cytotoxic T lymphocytes and interferon-γ in coronavirus infection: Lessons from murine coronavirus infections in mice

Murine coronavirus (CoV) is a beta-CoV that infects mice by binding to carcinoembryonic antigen-related cell adhesion molecule 1. Intraperitoneal infection with the murine CoV strain JHM (JHMV) induces acute mild hepatitis in mice. While both innate and acquired immune responses play a significant role in the protection against murine CoV infection in mice, CD8⁺ cytotoxic T lymphocytes (CTLs) and interferon-γ are essential for viral clearance in JHMV-induced hepatitis. In addition, CoVs are characterized by high diversity, caused by mutations, recombination, and gene gain/loss. 25V16G is an immune-escape JHMV variant, which lacks a dominant CTL epitope. By evading immune responses, 25V16G establishes persistent infections, leading to granulomatous serositis in interferon-γ-deficient mice. These examples of CoV-associated pathogenesis in mice might provide useful information on other CoV infections, including coronavirus disease 2019 (COVID-19).