Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1995 Apr;39(4):846–849. doi: 10.1128/aac.39.4.846

Antiviral effect of oryzacystatin, a proteinase inhibitor in rice, against herpes simplex virus type 1 in vitro and in vivo.

H Aoki 1, T Akaike 1, K Abe 1, M Kuroda 1, S Arai 1, R Okamura 1, A Negi 1, H Maeda 1
PMCID: PMC162640  PMID: 7785982

Abstract

Oryzacystatin (OC) is the first-described cystatin originating from rice seed; it consists of two molecular species, OC-I and OC-II, which have antiviral action against poliovirus in vitro (H. Kondo, S. Ijiri, K. Abe, H. Maeda, and S. Arai, FEBS Lett. 299:48-50, 1992). In the experiments reported here, we investigated the effects of OC-I and OC-II on the replication of herpes simplex virus type 1 (HSV-1) in vitro and in vivo. HSV-1 was inoculated onto monolayers of monkey kidney epithelial cells (CV-1 cells) at a multiplicity of infection of 0.1 PFU per cell. After adsorption of the virus onto cells, the cultures were incubated in the presence of either OC-I or OC-II in the concentration range of 1.0 to 300 microM, and the supernatant virus yield was quantitated at 24 h. The effective concentration for 90% inhibition of HSV-1 was 14.8 microM, while a cytotoxic effect on CV-1 cells without infection of HSV-1 was not observed below 500 microM OC-I. Therefore, the apparent in vitro chemotherapeutic index was estimated to be more than 33. In the mouse model of HSV-1-induced keratitis and encephalopathy, topical administration of OC-I to the mouse cornea produced a significant decrease in virus production in the cornea (mean virus yields: 3.11 log10 PFU in the treated group and 4.37 log10 PFU in the control group) and significant improvement in survival rates (P = 0.01). The in vivo antiherpetic effect of OC-I was comparable to that of acyclovir, indicating that topical treatment of HSV-1 infection in humans with OC-I might be possible. Our data also suggest the importance of some thiol proteinases, which may be derived from either the host's cells or HSV-1, during the replication process of HSV-1.

Full Text

The Full Text of this article is available as a PDF (182.6 KB).

Selected References

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

  1. Abe K., Emori Y., Kondo H., Suzuki K., Arai S. Molecular cloning of a cysteine proteinase inhibitor of rice (oryzacystatin). Homology with animal cystatins and transient expression in the ripening process of rice seeds. J Biol Chem. 1987 Dec 15;262(35):16793–16797. [PubMed] [Google Scholar]
  2. Abe M., Abe K., Iwabuchi K., Domoto C., Arai S. Corn cystatin I expressed in Escherichia coli: investigation of its inhibitory profile and occurrence in corn kernels. J Biochem. 1994 Sep;116(3):488–492. doi: 10.1093/oxfordjournals.jbchem.a124551. [DOI] [PubMed] [Google Scholar]
  3. Abe M., Abe K., Kuroda M., Arai S. Corn kernel cysteine proteinase inhibitor as a novel cystatin superfamily member of plant origin. Molecular cloning and expression studies. Eur J Biochem. 1992 Nov 1;209(3):933–937. doi: 10.1111/j.1432-1033.1992.tb17365.x. [DOI] [PubMed] [Google Scholar]
  4. Akaike T., Maeda H., Maruo K., Sakata Y., Sato K. Potentiation of infectivity and pathogenesis of influenza A virus by a house dust mite protease. J Infect Dis. 1994 Oct;170(4):1023–1026. doi: 10.1093/infdis/170.4.1023. [DOI] [PubMed] [Google Scholar]
  5. Akaike T., Molla A., Ando M., Araki S., Maeda H. Molecular mechanism of complex infection by bacteria and virus analyzed by a model using serratial protease and influenza virus in mice. J Virol. 1989 May;63(5):2252–2259. doi: 10.1128/jvi.63.5.2252-2259.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Björck L., Grubb A., Kjellén L. Cystatin C, a human proteinase inhibitor, blocks replication of herpes simplex virus. J Virol. 1990 Feb;64(2):941–943. doi: 10.1128/jvi.64.2.941-943.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Croen K. D. Evidence for antiviral effect of nitric oxide. Inhibition of herpes simplex virus type 1 replication. J Clin Invest. 1993 Jun;91(6):2446–2452. doi: 10.1172/JCI116479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Darke P. L., Chen E., Hall D. L., Sardana M. K., Veloski C. A., LaFemina R. L., Shafer J. A., Kuo L. C. Purification of active herpes simplex virus-1 protease expressed in Escherichia coli. J Biol Chem. 1994 Jul 22;269(29):18708–18711. [PubMed] [Google Scholar]
  9. Deckman I. C., Hagen M., McCann P. J., 3rd Herpes simplex virus type 1 protease expressed in Escherichia coli exhibits autoprocessing and specific cleavage of the ICP35 assembly protein. J Virol. 1992 Dec;66(12):7362–7367. doi: 10.1128/jvi.66.12.7362-7367.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Inoue Y., Ohashi Y., Shimomura Y., Manabe R., Yamada M., Ueda S., Kato S. Herpes simplex virus glycoprotein D. Protective immunity against murine herpetic keratitis. Invest Ophthalmol Vis Sci. 1990 Mar 1;31(3):411–418. [PubMed] [Google Scholar]
  11. Klenk H. D., Garten W. Host cell proteases controlling virus pathogenicity. Trends Microbiol. 1994 Feb;2(2):39–43. doi: 10.1016/0966-842x(94)90123-6. [DOI] [PubMed] [Google Scholar]
  12. Kondo H., Abe K., Nishimura I., Watanabe H., Emori Y., Arai S. Two distinct cystatin species in rice seeds with different specificities against cysteine proteinases. Molecular cloning, expression, and biochemical studies on oryzacystatin-II. J Biol Chem. 1990 Sep 15;265(26):15832–15837. [PubMed] [Google Scholar]
  13. Kondo H., Ijiri S., Abe K., Maeda H., Arai S. Inhibitory effect of oryzacystatins and a truncation mutant on the replication of poliovirus in infected Vero cells. FEBS Lett. 1992 Mar 24;299(1):48–50. doi: 10.1016/0014-5793(92)80097-z. [DOI] [PubMed] [Google Scholar]
  14. Liu F. Y., Roizman B. The herpes simplex virus 1 gene encoding a protease also contains within its coding domain the gene encoding the more abundant substrate. J Virol. 1991 Oct;65(10):5149–5156. doi: 10.1128/jvi.65.10.5149-5156.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ohashi Y., Sakaue Y., Kato S., Wada T., Sato K. A detergent-soluble extract of virus-infected cells free from infectious virus protects mice from lethal herpes simplex virus infection. Biken J. 1980 Dec;23(4):199–204. [PubMed] [Google Scholar]
  16. Preston V. G., Rixon F. J., McDougall I. M., McGregor M., al Kobaisi M. F. Processing of the herpes simplex virus assembly protein ICP35 near its carboxy terminal end requires the product of the whole of the UL26 reading frame. Virology. 1992 Jan;186(1):87–98. doi: 10.1016/0042-6822(92)90063-u. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES