Differential cleavage of viral polypeptides by allotypic variants of granzyme B skews immunity to mouse cytomegalovirus

Sutton, Vivien R.; Andoniou, Christopher E.; Leeming, Michael G.; House, Colin M.; Watt, Sally V.; Verschoor, Sandra; Ciccone, Annette; Voskoboinik, Ilia; Degli-Esposti, Mariapia A.; Trapani, Joseph A.

doi:10.1016/j.bbapap.2020.140457

Cited by 2 publications

(2 citation statements)

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“…18 In mice, genetic variation in the GzmB gene correlated with the likelihood of death because of murine cytomegalovirus infection. 19 Most of the data on cytotoxic effector proteins in NK cells and CTLs are derived from model organisms, namely humans and laboratory rodents. Much less is known about these important immune mechanisms, their molecules, and their genes in other mammals.…”

Section: Introductionmentioning

confidence: 99%

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The deadly face of felid killer cells: The cytotoxic proteins and their genes

Futas

Oppelt

Vychodilova

et al. 2022

HLA

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Natural killer cells and cytotoxic T lymphocytes are the main cell populations of the immune system able to directly kill target cells via cytotoxic granules. Different mammalian species may differ in specific features of their pore‐forming protein (perforin) and granule‐bound serine proteases (granzymes). One perforin gene (PRF1) and four genes encoding granzymes A, B, H, and K (GZMA, GZMB, GZMH, GZMK) were identified in the reference genomes of felids. The objective of this work was to characterize the genes PRF1, GZMA and GZMB in a panel of 17 felid species by next‐generation re‐sequencing. A search of available felid genomes (17 species) retrieved the coding sequences of these genes for comparison to our data. Both sets of sequences or their combinations (23 species) were used for phylogenetic and selection analyses. Nucleotide PRF1, GZMA and GZMB sequences showed high similarities between felid species (over 95% identity). All trees derived from coding sequences expressed phylogenetic relationships corresponding to the zoological taxonomy of the Felidae, except GZMA. No effects of positive selection were detected in the genes studied, however, effects of purifying selection were observed for PRF1 and GZMA. The conservation of PRF1 is in agreement with its critical biological function. The differentiation observed between granzyme sub‐families may reflect an adaptation to pathogen variation. The need to maintain important gene functions and at the same time cope with various pathogens may lead to an equilibrium between positive and negative selective pressures acting on GZMB. The within‐species variability in wild felid populations merits further investigation.

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Section: Introductionmentioning

confidence: 99%

“…GZMB haplotypes are also associated with natural killer cell cytotoxicity 18 . In mice, genetic variation in the GzmB gene correlated with the likelihood of death because of murine cytomegalovirus infection 19 …”

Section: Introductionmentioning

confidence: 99%