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Reovirus-induced apoptosis is preceded by increased cellular calpain activity and is blocked by calpain inhibitors.

Debiasi RL, Squier MK, Pike B, Wynes M, Dermody TS, Cohen JJ, Tyler KL
J Virol. 1999 73 (1): 695-701

PMID: 9847375 · PMCID: PMC103876 · DOI:10.1128/JVI.73.1.695-701.1999

The cellular pathways of apoptosis have not been fully characterized; however, calpain, a cytosolic calcium-activated cysteine protease, has been implicated in several forms of programmed cell death. Reoviruses induce apoptosis both in vitro and in vivo and serve as a model for studying virus-induced cell death. We investigated the potential role of calpain in reovirus-induced apoptosis in vitro by measuring calpain activity as well as evaluating the effects of calpain inhibitors. L929 cells were infected with reovirus type 3 Abney (T3A), and calpain activity, measured as cleavage of the fluorogenic calpain substrate Suc-Leu-Leu-Val-Tyr-AMC, was monitored. There was a 1.6-fold increase in calpain activity in T3A-infected cells compared to mock-infected cells; this increase was completely inhibited by preincubation with calpain inhibitor I (N-acetyl-leucyl-leucyl-norleucinal [aLLN]), an active-site inhibitor. Both aLLN and PD150606, a specific calpain inhibitor that interacts with the calcium-binding site, inhibited reovirus-induced apoptosis in L929 cells by 54 to 93%. Apoptosis induced by UV-inactivated reovirus was also reduced 65 to 69% by aLLN, indicating that inhibition of apoptosis by calpain inhibitors is independent of effects on viral replication. We conclude that calpain activation is a component of the regulatory cascade in reovirus-induced apoptosis.

MeSH Terms (9)

Acrylates Animals Apoptosis Calpain Cysteine Proteinase Inhibitors Mice Reoviridae Signal Transduction Ultraviolet Rays

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