Fig 1.
Schematic overview of the noncytotoxic functions of Gzms in viral infection.
CLs secrete perforin and Gzms into the immunological synapse. Perforin pores mediate Gzm entry in the target cell (1). Gzms cleave and (in)activate viral proteins (2) and host cell proteins inside the cytoplasm and the nucleus necessary for viral entry (3), replication, protein synthesis, virion assembly (4), and viral release (5). CLs and also other cell types (e.g., macrophages) can directly secrete Gzms in the microenvironment. These extracellular Gzms can induce pro-inflammatory cytokine release by multiple cell types, such as monocytes, macrophages, DCs, mast cells, fibroblasts, and epithelial cells, further supporting the antiviral immune response (6). Created with BioRender.com. CL, cytotoxic lymphocyte; DC, dendritic cell; Gzm, granzyme.
Table 1.
Validated Gzm substrates affecting viral replication upon cleavage.