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Updated: Sep 28, 2026
A Colorimetric Assay that Specifically Measures Granzyme B Proteolytic Activity: Hydrolysis of Boc-Ala-Ala-Asp-S-Bzl
Published on: November 28, 2014
Control of lymphocytic choriomeningitis virus infection in granzyme B deficient mice
Allan J Zajac1, John M Dye, Daniel G Quinn
1Department of Microbiology and Immunology, Loyola University Chicago, Maywood, Illinois 60153, USA.
Abstract:
We have investigated whether granzyme B (GzmB) is required for effective cytotoxic T lymphocyte (CTL) mediated control of lymphocytic choriomeningitis virus (LCMV) infection. Clearance of LCMV from tissues of GzmB-deficient (GzmB-) mice following intraperitoneal infection with LCMV was impaired compared with control mice; however, the virus was ultimately eliminated. The impaired clearance of LCMV in GzmB- mice was not due to a deficiency in the generation of LCMV-specific T cells. In addition, CTL from LCMV-infected GzmB- mice efficiently lysed virus-infected cells in vitro, but were deficient in their ability to induce rapid DNA fragmentation in target cells. We examined whether the development of protective immunity against intracranial (i.c.) rechallenge with LCMV was compromised in GzmB- mice. We found that clearance of LCMV from the brain following secondary i.c. infection also was slower in the absence of GzmB; however, the virus was ultimately eliminated and the mice survived. Our data indicate that clearance of LCMV is delayed in the absence of GzmB expression, but that other CTL effector molecules can compensate for the absence of this granule constituent in vivo.
Insights
Granzyme B (GzmB) deficiency in mice delayed lymphocytic choriomeningitis virus (LCMV) clearance but did not prevent viral elimination, indicating compensatory immune mechanisms in cytotoxic T lymphocyte (CTL) responses.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Cytotoxic T lymphocytes (CTLs) are crucial for controlling viral infections.
- Granzyme B (GzmB) is a key effector molecule used by CTLs to induce target cell death.
- The specific role of GzmB in CTL-mediated control of lymphocytic choriomeningitis virus (LCMV) remains incompletely understood.
Purpose of the Study:
- To investigate the necessity of granzyme B (GzmB) for effective cytotoxic T lymphocyte (CTL) mediated control of lymphocytic choriomeningitis virus (LCMV) infection.
- To determine if GzmB deficiency impacts viral clearance, T cell generation, and protective immunity following LCMV infection.
Main Methods:
- Comparison of LCMV clearance in GzmB-deficient (GzmB-) mice and control mice following intraperitoneal infection.
- Assessment of LCMV-specific T cell generation and CTL lytic activity in vitro.
- Evaluation of viral clearance and survival following secondary intracranial (i.c.) LCMV rechallenge.
Main Results:
- LCMV clearance from tissues was impaired but not abolished in GzmB- mice.
- CTLs from GzmB- mice showed normal in vitro lysis but reduced DNA fragmentation induction.
- Secondary LCMV infection clearance was slower in GzmB- mice, yet ultimately successful, with survival.
Conclusions:
- Granzyme B (GzmB) expression contributes to, but is not essential for, efficient LCMV clearance by CTLs.
- Absence of GzmB leads to delayed viral control, suggesting compensatory roles for other CTL effector mechanisms in vivo.
- Effective anti-viral immunity against LCMV can be established even in the absence of granzyme B.
