The cysteine protease inhibitors cystatins inhibit herpes simplex virus type 1-induced apoptosis and virus yield in HEp-2 cells

Author:

Peri Piritta1,Hukkanen Veijo21,Nuutila Kristiina3,Saukko Pekka3,Abrahamson Magnus4,Vuorinen Tytti1

Affiliation:

1. Department of Virology, University of Turku, Finland

2. Department of Microbiology, University of Oulu, Finland

3. Department of Forensic Medicine, University of Turku, Finland

4. Department of Laboratory Medicine, University of Lund, Sweden

Abstract

The role of cystatins in herpes simplex virus (HSV)-induced apoptosis and viral replication has been studied. Human epithelial (HEp-2) cells infected with wild-type HSV-1 (F), with a deletion virus lacking the anti-apoptotic gene Us3 (R7041) or with a deletion virus lacking the anti-apoptotic genes Us3 and ICP4 (d120) were treated with cystatin A, C or D. Cells and culture media were studied at different time points for replicating HSV-1 and for apoptosis. Cystatins C and D inhibited the yield of replicative HSV-1 significantly in HEp-2 cells. In addition, cystatin D inhibited R7041 and d120 virus-induced apoptosis. Moreover, cystatin A inhibited R7041-induced apoptosis. These inhibitory effects of cystatins on virus replication and apoptosis are likely to be separate functions. Cystatin D treatment decreased cellular cathepsin B activity in HSV-1 infection, suggesting that cathepsin B is involved in virus-induced apoptosis.

Publisher

Microbiology Society

Subject

Virology

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