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. 1990 Feb;64(2):941–943. doi: 10.1128/jvi.64.2.941-943.1990

Cystatin C, a human proteinase inhibitor, blocks replication of herpes simplex virus.

L Björck 1, A Grubb 1, L Kjellén 1
PMCID: PMC249195  PMID: 2153254

Abstract

Cystatin C is a human cysteine proteinase inhibitor present in extracellular fluids. Cystatin C and a tripeptide derivative (Z-LVG-CHN2) that mimics its proteinase-binding center, were tested for possible antiviral activity against herpes simplex virus type 1 (HSV) and poliovirus type 1. Both recombinant cystatin C and Z-LVG-CHN2 displayed strong inhibitory effects on HSV replication, whereas no significant effect on poliovirus replication was seen. The molar concentration of cystatin C that gave total inhibition of HSV replication was lower than that of either Z-LVG-CHN2 or of acyclovir, the drug currently most used against HSV infections. These results suggest that cysteine proteinase inhibitors might play a physiological role as inhibitors of viral replication and that such proteinase inhibitors, or peptide derivatives that mimic their proteinase-binding centers, might be used as antiviral agents.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abrahamson M., Barrett A. J., Salvesen G., Grubb A. Isolation of six cysteine proteinase inhibitors from human urine. Their physicochemical and enzyme kinetic properties and concentrations in biological fluids. J Biol Chem. 1986 Aug 25;261(24):11282–11289. [PubMed] [Google Scholar]
  2. Abrahamson M., Dalbøge H., Olafsson I., Carlsen S., Grubb A. Efficient production of native, biologically active human cystatin C by Escherichia coli. FEBS Lett. 1988 Aug 15;236(1):14–18. doi: 10.1016/0014-5793(88)80276-x. [DOI] [PubMed] [Google Scholar]
  3. Abrahamson M., Grubb A., Olafsson I., Lundwall A. Molecular cloning and sequence analysis of cDNA coding for the precursor of the human cysteine proteinase inhibitor cystatin C. FEBS Lett. 1987 Jun 1;216(2):229–233. doi: 10.1016/0014-5793(87)80695-6. [DOI] [PubMed] [Google Scholar]
  4. Abrahamson M., Ritonja A., Brown M. A., Grubb A., Machleidt W., Barrett A. J. Identification of the probable inhibitory reactive sites of the cysteine proteinase inhibitors human cystatin C and chicken cystatin. J Biol Chem. 1987 Jul 15;262(20):9688–9694. [PubMed] [Google Scholar]
  5. Barrett A. J., Davies M. E., Grubb A. The place of human gamma-trace (cystatin C) amongst the cysteine proteinase inhibitors. Biochem Biophys Res Commun. 1984 Apr 30;120(2):631–636. doi: 10.1016/0006-291x(84)91302-0. [DOI] [PubMed] [Google Scholar]
  6. Bazan J. F., Fletterick R. J. Viral cysteine proteases are homologous to the trypsin-like family of serine proteases: structural and functional implications. Proc Natl Acad Sci U S A. 1988 Nov;85(21):7872–7876. doi: 10.1073/pnas.85.21.7872. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Green G. D., Shaw E. Peptidyl diazomethyl ketones are specific inactivators of thiol proteinases. J Biol Chem. 1981 Feb 25;256(4):1923–1928. [PubMed] [Google Scholar]
  8. Johansson P. J., Kjellén L. Inhibition of herpes simplex virus growth caused by preparations of animal immunoglobulins is not dependent on Fc-Fc receptor interactions. Intervirology. 1988;29(6):334–338. doi: 10.1159/000150064. [DOI] [PubMed] [Google Scholar]
  9. Korant B. D., Brzin J., Turk V. Cystatin, a protein inhibitor of cysteine proteases alters viral protein cleavages in infected human cells. Biochem Biophys Res Commun. 1985 Mar 29;127(3):1072–1076. doi: 10.1016/s0006-291x(85)80054-1. [DOI] [PubMed] [Google Scholar]
  10. Kräusslich H. G., Wimmer E. Viral proteinases. Annu Rev Biochem. 1988;57:701–754. doi: 10.1146/annurev.bi.57.070188.003413. [DOI] [PubMed] [Google Scholar]
  11. Marks N., Berg M. J., Benuck M. Preferential action of rat brain cathepsin B as a peptidyl dipeptidase converting pro-opioid oligopeptides. Arch Biochem Biophys. 1986 Sep;249(2):489–499. doi: 10.1016/0003-9861(86)90026-3. [DOI] [PubMed] [Google Scholar]
  12. Palmenberg A. C., Pallansch M. A., Rueckert R. R. Protease required for processing picornaviral coat protein resides in the viral replicase gene. J Virol. 1979 Dec;32(3):770–778. doi: 10.1128/jvi.32.3.770-778.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Taugner R., Bührle C. P., Nobiling R., Kirschke H. Coexistence of renin and cathepsin B in epithelioid cell secretory granules. Histochemistry. 1985;83(2):103–108. doi: 10.1007/BF00495138. [DOI] [PubMed] [Google Scholar]

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