Mice with a newly identified germline mutation suggest that a fatal genetic disease in humans might be triggered by viral infection, according to Crozat et al. (page 853).
The mutated gene, called Unc13d, was identified in a screen for chemically induced mutations that make mice susceptible to murine cytomegalovirus (MCMV). Mutations in the Unc13d orthologue MUNC13-4 are associated with a severe human disease characterized by the uncontrolled proliferation of CD8+ T cells. These cells produce cytokines but fail to release cytotoxic granules, as MUNC13-4 is required for the fusion of granules with the plasma membrane.
The Unc13d-deficient mice, which the team called Jinx, also had the same degranulation defect in their CD8+ T cells. They did not, however, develop the fatal lymphoproliferative disease seen in humans unless they were also infected with lymphochoriomeningitis virus—a pathogen that elicits robust T cell...
