Granzyme H destroys the function of critical adenoviral
proteins required for viral DNA replication and granzyme
B inhibition.
這是在2007 the EMBO journal 所發表的文章
summery:
Granzymes are key components of the immune response that play
important roles in eliminating host cells infected by intracellular
pathogens. Several granzymes are potent inducers of cell death.
However, whether granzymes use additional mechanisms to exert their
antipathogen activity remains elusive. Here, we show that in adenovirus-
infected cells in which granzyme B (gzmB) and downstream apoptosis pathways
are inhibited, granzyme H (gzmH), an orphan granzyme without known function,
directly cleaves the adenovirus DNA-binding protein (DBP), a viral component
absolutely required for viral DNA replication.
We directly addressed the functional consequences of the cleavage of the
DBP by gzmH through the generation of a virus that encodes a gzmH-resistant
DBP. This virus demonstrated that gzmH directly induces an important decay
in viral DNA replication. Interestingly, gzmH also cleaves the adenovirus
100K assembly protein, a major inhibitor of gzmB, and relieves gzmB inhibition.
These results provide the first evidence that granzymes can mediate antiviral
activity through direct cleavage of viral substrates, and further suggest that
different granzymes have synergistic functions to outflank viral defenses that
block host antiviral activites.
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