Noncytotoxic functions of killer cell granzymes in viral infections.
Cytotoxic lymphocytes produce granules armed with a set of 5 serine proteases (granzymes (Gzms)), which, together with the pore-forming protein (perforin), serve as a major defense against viral infections in humans. This granule-exocytosis pathway subsumes a well-established mechanism in which targ...
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oai:doaj.org-article:457ae3a589ce4f15a2f5f66d5c90e0e52021-12-02T20:00:09ZNoncytotoxic functions of killer cell granzymes in viral infections.1553-73661553-737410.1371/journal.ppat.1009818https://doaj.org/article/457ae3a589ce4f15a2f5f66d5c90e0e52021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009818https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Cytotoxic lymphocytes produce granules armed with a set of 5 serine proteases (granzymes (Gzms)), which, together with the pore-forming protein (perforin), serve as a major defense against viral infections in humans. This granule-exocytosis pathway subsumes a well-established mechanism in which target cell death is induced upon perforin-mediated entry of Gzms and subsequent activation of various (apoptosis) pathways. In the past decade, however, a growing body of evidence demonstrated that Gzms also inhibit viral replication and potential reactivation in cell death-independent manners. For example, Gzms can induce proteolysis of viral or host cell proteins necessary for the viral entry, release, or intracellular trafficking, as well as augment pro-inflammatory antiviral cytokine response. In this review, we summarize current evidence for the noncytotoxic mechanisms and roles by which killer cells can use Gzms to combat viral infections, and we discuss the potential thereof for the development of novel therapies.Lisanne C de JongSandra CrnkoToine Ten BroekeNiels BovenschenPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 9, p e1009818 (2021) |
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Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Lisanne C de Jong Sandra Crnko Toine Ten Broeke Niels Bovenschen Noncytotoxic functions of killer cell granzymes in viral infections. |
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Cytotoxic lymphocytes produce granules armed with a set of 5 serine proteases (granzymes (Gzms)), which, together with the pore-forming protein (perforin), serve as a major defense against viral infections in humans. This granule-exocytosis pathway subsumes a well-established mechanism in which target cell death is induced upon perforin-mediated entry of Gzms and subsequent activation of various (apoptosis) pathways. In the past decade, however, a growing body of evidence demonstrated that Gzms also inhibit viral replication and potential reactivation in cell death-independent manners. For example, Gzms can induce proteolysis of viral or host cell proteins necessary for the viral entry, release, or intracellular trafficking, as well as augment pro-inflammatory antiviral cytokine response. In this review, we summarize current evidence for the noncytotoxic mechanisms and roles by which killer cells can use Gzms to combat viral infections, and we discuss the potential thereof for the development of novel therapies. |
format |
article |
author |
Lisanne C de Jong Sandra Crnko Toine Ten Broeke Niels Bovenschen |
author_facet |
Lisanne C de Jong Sandra Crnko Toine Ten Broeke Niels Bovenschen |
author_sort |
Lisanne C de Jong |
title |
Noncytotoxic functions of killer cell granzymes in viral infections. |
title_short |
Noncytotoxic functions of killer cell granzymes in viral infections. |
title_full |
Noncytotoxic functions of killer cell granzymes in viral infections. |
title_fullStr |
Noncytotoxic functions of killer cell granzymes in viral infections. |
title_full_unstemmed |
Noncytotoxic functions of killer cell granzymes in viral infections. |
title_sort |
noncytotoxic functions of killer cell granzymes in viral infections. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2021 |
url |
https://doaj.org/article/457ae3a589ce4f15a2f5f66d5c90e0e5 |
work_keys_str_mv |
AT lisannecdejong noncytotoxicfunctionsofkillercellgranzymesinviralinfections AT sandracrnko noncytotoxicfunctionsofkillercellgranzymesinviralinfections AT toinetenbroeke noncytotoxicfunctionsofkillercellgranzymesinviralinfections AT nielsbovenschen noncytotoxicfunctionsofkillercellgranzymesinviralinfections |
_version_ |
1718375717455003648 |