A Natural Genetic Variant of Granzyme B Confers Lethality to a Common Viral Infection

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Granzymes (Gzm) are serine proteases expressed by cytotoxic T cells and natural killer cells, and are important for the destruction of virally infected cells. To date, the function of these molecules has been assessed exclusively in common laboratory mouse strains that express identical granzyme proteins. In wild mouse populations, variants of granzyme B have been identified, but how these function, especially in the context of infections, is unknown. We have generated a novel mouse strain expressing a granzyme B variant found in wild mice (GzmBW), and exposed these mice to viral infections. The substrates cleaved by GzmBW were found to differ significantly from those cleaved by the GzmBP protein, which is normally expressed by laboratory mice. Alterations in substrate specificity resulted in GzmBW mice being significantly more susceptible to infection with murine cytomegalovirus, a common mouse pathogen. Our findings demonstrate that polymorphisms in granzyme B can profoundly affect the outcome of infections with some viral pathogens.

Vyšlo v časopise: A Natural Genetic Variant of Granzyme B Confers Lethality to a Common Viral Infection. PLoS Pathog 10(12): e32767. doi:10.1371/journal.ppat.1004526
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004526

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