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Journal of Virology, February 2008, p. 1581-1590, Vol. 82, No. 3
0022-538X/08/$08.00+0     doi:10.1128/JVI.01375-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Calpain 1 and 2 Are Required for RNA Replication of Echovirus 1

Paula Upla,¹ Varpu Marjomäki,¹ Liisa Nissinen,² Camilla Nylund,⁴ Matti Waris,³ Timo Hyypiä,³ and Jyrki Heino^4*

Nanoscience Center/Department of Biological and Environmental Science, University of Jyväskylä, FI-40351 Jyväskylä, Finland,¹ Biotie Therapies, FI-20520 Turku, Finland,² Department of Virology, University of Turku, FI-20520 Turku, Finland,³ Department of Biochemistry and Food Chemistry, University of Turku, FI-20520 Turku, Finland⁴

Received 25 June 2007/ Accepted 12 November 2007

Calpains are calcium-dependent cysteine proteases that degrade cytoskeletal and cytoplasmic proteins. We have studied the role of calpains in the life cycle of human echovirus 1 (EV1). The calpain inhibitors, including calpeptin, calpain inhibitor 1, and calpain inhibitor 2 as well as calpain 1 and calpain 2 short interfering RNAs, completely blocked EV1 infection in the host cells. The effect of the inhibitors was not specific for EV1, because they also inhibited infection by other picornaviruses, namely, human parechovirus 1 and coxsackievirus B3. The importance of the calpains in EV1 infection also was supported by the fact that EV1 increased calpain activity 3 h postinfection. Confocal microscopy and immunoelectron microscopy showed that the EV1/caveolin-1-positive vesicles also contain calpain 1 and 2. Our results indicate that calpains are not required for virus entry but that they are important at a later stage of infection. Calpain inhibitors blocked the production of EV1 particles after microinjection of EV1 RNA into the cells, and they effectively inhibited the synthesis of viral RNA in the host cells. Thus, both calpain 1 and calpain 2 are essential for the replication of EV1 RNA.

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* Corresponding author. Mailing address: Department of Biochemistry and Food Chemistry, University of Turku, FI-20520 Turku, Finland. Phone: 358 2 333 6879. Fax: 358 2 333 6860. E-mail address: jyrki.heino{at}utu.fi

Published ahead of print on 21 November 2007.

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Journal of Virology, February 2008, p. 1581-1590, Vol. 82, No. 3
0022-538X/08/$08.00+0     doi:10.1128/JVI.01375-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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