Significance T cell exhaustion and successful therapy to restore T cell function initially uncovered with lymphocytic choriomeningitis virus (LCMV) Clone (Cl) 13 infection is important for understanding and treating persistent viral infections and cancers in mice and humans. Here, we report that Cl 13 infection in multiple inbred mouse strains elicits opposite phenotypes: acute death in 7 to 9 d associated with a robust T cell response contrasted to suppression of T cell response leading to persistent infection with normal life span. Death was due to pulmonary vascular leakage of fluids and cells into the lung, leading to respiratory failure. Death can be aborted by blocking interferon-1 signaling or deleting CD8 T cells.