Granzymes are the essential downstream effector molecules for the control of primary virus infections by cytolytic

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A High Yield and Cost-efficient Expression System of Human Granzymes in Mammalian Cells
09:16

A High Yield and Cost-efficient Expression System of Human Granzymes in Mammalian Cells

Published on: June 10, 2015

A Müllbacher1, P Waring, R Tha Hla

  • 1Division of Immunology, John Curtin School of Medical Research, Australian National University, Canberra ACT 2601, Australia. arno.mullbacher@anu.edu.au

Proceedings of the National Academy of Sciences of the United States of America
|November 26, 1999
PubMed

Insights

Granzyme A and Granzyme B are essential for controlling viral infections. Mice lacking these granzymes, alongside perforin, cannot fight ectromelia virus, highlighting their crucial role in immune defense.

Area of Science:

  • Immunology
  • Virology
  • Cellular Biology

Background:

  • Perforin is a key molecule in T cell-mediated viral control.
  • Cytolytic vesicles contain perforin, granzyme A (gzmA), and granzyme B (gzmB).

Purpose of the Study:

  • To investigate the roles of gzmA and gzmB in host defense against viral pathogens.
  • To determine if gzmA and gzmB are essential for controlling ectromelia virus infection.

Main Methods:

  • Utilized gzmAxgzmB double knockout mice.
  • Assessed control of primary ectromelia virus infection in these mice.
  • Evaluated perforin expression and splenic cytolytic T cell generation.

Main Results:

  • Mice lacking gzmA and gzmB were unable to control ectromelia virus infection.
  • These mice showed dose-dependent mortality despite functional perforin and intact cytolytic T cell generation.
  • The absence of gzmA and gzmB rendered mice as susceptible as perforin-deficient mice.

Conclusions:

  • Granzyme A and Granzyme B are indispensable effector molecules for host defense against viral pathogens.
  • GzmA and gzmB act in concert with perforin in granule exocytosis-mediated immunity.
  • These granzymes are critical for controlling natural viral infections, not just perforin alone.

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