The cysteine protease inhibitors cystatins inhibit herpes simplex virus type 1-induced apoptosis and virus yield in HEp-2 cells.
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.
Peri
Piritta
P
Department of Virology, University of Turku, Finland.
Hukkanen
Veijo
V
Department of Microbiology, University of Oulu, Finland.|Department of Virology, University of Turku, Finland.
Nuutila
Kristiina
K
Department of Forensic Medicine, University of Turku, Finland.
Saukko
Pekka
P
Department of Forensic Medicine, University of Turku, Finland.
Abrahamson
Magnus
M
Department of Laboratory Medicine, University of Lund, Sweden.
Vuorinen
Tytti
T
Department of Virology, University of Turku, Finland.
D017209:Apoptosis / Q000187:drug effects; D002401:Cathepsin B / Q000502:physiology; D002460:Cell Line; D015891:Cystatins / Q000302:isolation & purification / Q000494:pharmacology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D017353:Gene Deletion; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects
D015891:Cystatins; D015853:Cysteine Proteinase Inhibitors; D017874:Immediate-Early Proteins; D014764:Viral Proteins; C048925:herpes simplex virus, type 1 protein ICP4; D017346:Protein Serine-Threonine Kinases; C095207:US3 protein, Human herpesvirus 1; D002401:Cathepsin B