Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1993 Jun;67(6):3601–3604. doi: 10.1128/jvi.67.6.3601-3604.1993

Legitimate and illegitimate cleavage of human immunodeficiency virus glycoproteins by furin.

Y Morikawa 1, E Barsov 1, I Jones 1
PMCID: PMC237708  PMID: 8497067

Abstract

Coexpression of human immunodeficiency virus type 1 glycoproteins with the subtilisin-like protease furin leads to processing of gp160 and gp140, a truncated form of gp160, to gp120. In addition, we show that gp120 itself is further cleaved by furin at sites near the primary cleavage site and within the V3 loop.

Full text

PDF
3601

Images in this article

Selected References

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

  1. Balzarini J., Naesens L., Slachmuylders J., Niphuis H., Rosenberg I., Holý A., Schellekens H., De Clercq E. 9-(2-Phosphonylmethoxyethyl)adenine (PMEA) effectively inhibits retrovirus replication in vitro and simian immunodeficiency virus infection in rhesus monkeys. AIDS. 1991 Jan;5(1):21–28. doi: 10.1097/00002030-199101000-00003. [DOI] [PubMed] [Google Scholar]
  2. Barr P. J. Mammalian subtilisins: the long-sought dibasic processing endoproteases. Cell. 1991 Jul 12;66(1):1–3. doi: 10.1016/0092-8674(91)90129-m. [DOI] [PubMed] [Google Scholar]
  3. Bresnahan P. A., Leduc R., Thomas L., Thorner J., Gibson H. L., Brake A. J., Barr P. J., Thomas G. Human fur gene encodes a yeast KEX2-like endoprotease that cleaves pro-beta-NGF in vivo. J Cell Biol. 1990 Dec;111(6 Pt 2):2851–2859. doi: 10.1083/jcb.111.6.2851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Burnette W. N. "Western blotting": electrophoretic transfer of proteins from sodium dodecyl sulfate--polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A. Anal Biochem. 1981 Apr;112(2):195–203. doi: 10.1016/0003-2697(81)90281-5. [DOI] [PubMed] [Google Scholar]
  5. Clements G. J., Price-Jones M. J., Stephens P. E., Sutton C., Schulz T. F., Clapham P. R., McKeating J. A., McClure M. O., Thomson S., Marsh M. The V3 loops of the HIV-1 and HIV-2 surface glycoproteins contain proteolytic cleavage sites: a possible function in viral fusion? AIDS Res Hum Retroviruses. 1991 Jan;7(1):3–16. doi: 10.1089/aid.1991.7.3. [DOI] [PubMed] [Google Scholar]
  6. Fenouillet E., Gluckman J. C. Immunological analysis of human immunodeficiency virus type 1 envelope glycoprotein proteolytic cleavage. Virology. 1992 Apr;187(2):825–828. doi: 10.1016/0042-6822(92)90487-a. [DOI] [PubMed] [Google Scholar]
  7. Gotoh B., Ohnishi Y., Inocencio N. M., Esaki E., Nakayama K., Barr P. J., Thomas G., Nagai Y. Mammalian subtilisin-related proteinases in cleavage activation of the paramyxovirus fusion glycoprotein: superiority of furin/PACE to PC2 or PC1/PC3. J Virol. 1992 Nov;66(11):6391–6397. doi: 10.1128/jvi.66.11.6391-6397.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Haffar O. K., Nakamura G. R., Berman P. W. The carboxy terminus of human immunodeficiency virus type 1 gp160 limits its proteolytic processing and transport in transfected cell lines. J Virol. 1990 Jun;64(6):3100–3103. doi: 10.1128/jvi.64.6.3100-3103.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hallenberger S., Bosch V., Angliker H., Shaw E., Klenk H. D., Garten W. Inhibition of furin-mediated cleavage activation of HIV-1 glycoprotein gp160. Nature. 1992 Nov 26;360(6402):358–361. doi: 10.1038/360358a0. [DOI] [PubMed] [Google Scholar]
  10. Helseth E., Olshevsky U., Furman C., Sodroski J. Human immunodeficiency virus type 1 gp120 envelope glycoprotein regions important for association with the gp41 transmembrane glycoprotein. J Virol. 1991 Apr;65(4):2119–2123. doi: 10.1128/jvi.65.4.2119-2123.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hosaka M., Nagahama M., Kim W. S., Watanabe T., Hatsuzawa K., Ikemizu J., Murakami K., Nakayama K. Arg-X-Lys/Arg-Arg motif as a signal for precursor cleavage catalyzed by furin within the constitutive secretory pathway. J Biol Chem. 1991 Jul 5;266(19):12127–12130. [PubMed] [Google Scholar]
  12. Hwang S. S., Boyle T. J., Lyerly H. K., Cullen B. R. Identification of the envelope V3 loop as the primary determinant of cell tropism in HIV-1. Science. 1991 Jul 5;253(5015):71–74. doi: 10.1126/science.1905842. [DOI] [PubMed] [Google Scholar]
  13. Klimkait T., Strebel K., Hoggan M. D., Martin M. A., Orenstein J. M. The human immunodeficiency virus type 1-specific protein vpu is required for efficient virus maturation and release. J Virol. 1990 Feb;64(2):621–629. doi: 10.1128/jvi.64.2.621-629.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Leonard C. K., Spellman M. W., Riddle L., Harris R. J., Thomas J. N., Gregory T. J. Assignment of intrachain disulfide bonds and characterization of potential glycosylation sites of the type 1 recombinant human immunodeficiency virus envelope glycoprotein (gp120) expressed in Chinese hamster ovary cells. J Biol Chem. 1990 Jun 25;265(18):10373–10382. [PubMed] [Google Scholar]
  15. Marx J. How peptide hormones get ready for work. Science. 1991 May 10;252(5007):779–780. doi: 10.1126/science.1674172. [DOI] [PubMed] [Google Scholar]
  16. McCune J. M., Rabin L. B., Feinberg M. B., Lieberman M., Kosek J. C., Reyes G. R., Weissman I. L. Endoproteolytic cleavage of gp160 is required for the activation of human immunodeficiency virus. Cell. 1988 Apr 8;53(1):55–67. doi: 10.1016/0092-8674(88)90487-4. [DOI] [PubMed] [Google Scholar]
  17. Moore J. P., McKeating J. A., Jones I. M., Stephens P. E., Clements G., Thomson S., Weiss R. A. Characterization of recombinant gp120 and gp160 from HIV-1: binding to monoclonal antibodies and soluble CD4. AIDS. 1990 Apr;4(4):307–315. doi: 10.1097/00002030-199004000-00004. [DOI] [PubMed] [Google Scholar]
  18. Morikawa Y., Moore J. P., Fenouillet E., Jones I. M. Complementation of human immunodeficiency virus glycoprotein mutations in trans. J Gen Virol. 1992 Aug;73(Pt 8):1907–1913. doi: 10.1099/0022-1317-73-8-1907. [DOI] [PubMed] [Google Scholar]
  19. Morikawa Y., Moore J. P., Jones I. M. HIV-1 envelope protein gp120 expression by secretion in E. coli: assessment of CD4 binding and use in epitope mapping. J Virol Methods. 1990 Jul;29(1):105–113. doi: 10.1016/0166-0934(90)90013-6. [DOI] [PubMed] [Google Scholar]
  20. Morikawa Y., Overton H. A., Moore J. P., Wilkinson A. J., Brady R. L., Lewis S. J., Jones I. M. Expression of HIV-1 gp120 and human soluble CD4 by recombinant baculoviruses and their interaction in vitro. AIDS Res Hum Retroviruses. 1990 Jun;6(6):765–773. doi: 10.1089/aid.1990.6.765. [DOI] [PubMed] [Google Scholar]
  21. Nakayama K., Hosaka M., Hatsuzawa K., Murakami K. Cloning and functional expression of a novel endoprotease involved in prohormone processing at dibasic sites. J Biochem. 1991 Jun;109(6):803–806. doi: 10.1093/oxfordjournals.jbchem.a123461. [DOI] [PubMed] [Google Scholar]
  22. Overton H. A., Fujii Y., Price I. R., Jones I. M. The protease and gag gene products of the human immunodeficiency virus: authentic cleavage and post-translational modification in an insect cell expression system. Virology. 1989 May;170(1):107–116. doi: 10.1016/0042-6822(89)90357-7. [DOI] [PubMed] [Google Scholar]
  23. Pal R., Kalyanaraman V. S., Hoke G. M., Sarngadharan M. G. Processing and secretion of envelope glycoproteins of human immunodeficiency virus type 1 in the presence of trimming glucosidase inhibitor deoxynojirimycin. Intervirology. 1989;30(1):27–35. doi: 10.1159/000150073. [DOI] [PubMed] [Google Scholar]
  24. Ratner L., vander Heyden N., Dedera D. Inhibition of HIV and SIV infectivity by blockade of alpha-glucosidase activity. Virology. 1991 Mar;181(1):180–192. doi: 10.1016/0042-6822(91)90483-r. [DOI] [PubMed] [Google Scholar]
  25. Shioda T., Levy J. A., Cheng-Mayer C. Small amino acid changes in the V3 hypervariable region of gp120 can affect the T-cell-line and macrophage tropism of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9434–9438. doi: 10.1073/pnas.89.20.9434. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Stieneke-Gröber A., Vey M., Angliker H., Shaw E., Thomas G., Roberts C., Klenk H. D., Garten W. Influenza virus hemagglutinin with multibasic cleavage site is activated by furin, a subtilisin-like endoprotease. EMBO J. 1992 Jul;11(7):2407–2414. doi: 10.1002/j.1460-2075.1992.tb05305.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Wells D. E., Compans R. W. Expression and characterization of a functional human immunodeficiency virus envelope glycoprotein in insect cells. Virology. 1990 Jun;176(2):575–586. doi: 10.1016/0042-6822(90)90028-p. [DOI] [PubMed] [Google Scholar]
  28. Willey R. L., Maldarelli F., Martin M. A., Strebel K. Human immunodeficiency virus type 1 Vpu protein regulates the formation of intracellular gp160-CD4 complexes. J Virol. 1992 Jan;66(1):226–234. doi: 10.1128/jvi.66.1.226-234.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES