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. 1996 Mar 1;314(Pt 2):521–532. doi: 10.1042/bj3140521

Comparative cellular processing of the human immunodeficiency virus (HIV-1) envelope glycoprotein gp160 by the mammalian subtilisin/kexin-like convertases.

F Vollenweider 1, S Benjannet 1, E Decroly 1, D Savaria 1, C Lazure 1, G Thomas 1, M Chrétien 1, N G Seidah 1
PMCID: PMC1217081  PMID: 8670066

Abstract

We present here the pulse and pulse-chase analysis of the biosynthesis of the envelope glycoprotein gp160 and its intracellular processing by the subtilisin/kexin-like convertases furin, PACE4, PC1, PC5 and its isoform PC5/6-B. We demonstrate that furin and to a much lesser extent PACE4, PC5/6-B and PC1 are candidate enzymes capable of processing gp160 intracellularly. Furthermore we show that furin can also process gp160/gp120 into gp77/gp53 products by cleavage at the sequence RIQR/GPGR just preceding the conserved GPGR structure found at the tip of the hypervariable V3 loop. The results show that processing into gp120 could occur at or before the trans-Golgi network (TGN) where sulphation of the oligosaccharide moieties of gp160 was detected. In contrast, the formation of gp77/gp53 by furin is a late event occurring after exit from the TGN. Our data also revealed that the alpha glucosidase I inhibitor N-butyldeoxynojirimycin, although affecting the oligosaccharide composition of gp160, does not impair the processing of either gp160 or gp120 by either furin or PACE4. Finally, the co-expression of the [Arg355, Arg358]-alpha-1-antitrypsin Portland variant was shown to potently inhibit the processing of both gp160 and gp120 by these convertases.

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Selected References

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  1. Anderson E. D., Thomas L., Hayflick J. S., Thomas G. Inhibition of HIV-1 gp160-dependent membrane fusion by a furin-directed alpha 1-antitrypsin variant. J Biol Chem. 1993 Nov 25;268(33):24887–24891. [PubMed] [Google Scholar]
  2. Avril L. E., Di Martino-Ferrer M., Barin F., Gauthier F. Interaction between a membrane-associated serine proteinase of U-937 monocytes and peptides from the V3 loop of the human immunodeficiency virus type 1 (HIV-1) gp120 envelope glycoprotein. FEBS Lett. 1993 Feb 8;317(1-2):167–172. doi: 10.1016/0014-5793(93)81515-2. [DOI] [PubMed] [Google Scholar]
  3. Baeuerle P. A., Huttner W. B. Tyrosine sulfation is a trans-Golgi-specific protein modification. J Cell Biol. 1987 Dec;105(6 Pt 1):2655–2664. doi: 10.1083/jcb.105.6.2655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. Barr F. A., Leyte A., Mollner S., Pfeuffer T., Tooze S. A., Huttner W. B. Trimeric G-proteins of the trans-Golgi network are involved in the formation of constitutive secretory vesicles and immature secretory granules. FEBS Lett. 1991 Dec 9;294(3):239–243. doi: 10.1016/0014-5793(91)81438-e. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Benjannet S., Rondeau N., Day R., Chrétien M., Seidah N. G. PC1 and PC2 are proprotein convertases capable of cleaving proopiomelanocortin at distinct pairs of basic residues. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3564–3568. doi: 10.1073/pnas.88.9.3564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Benjannet S., Rondeau N., Paquet L., Boudreault A., Lazure C., Chrétien M., Seidah N. G. Comparative biosynthesis, covalent post-translational modifications and efficiency of prosegment cleavage of the prohormone convertases PC1 and PC2: glycosylation, sulphation and identification of the intracellular site of prosegment cleavage of PC1 and PC2. Biochem J. 1993 Sep 15;294(Pt 3):735–743. doi: 10.1042/bj2940735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Benjannet S., Savaria D., Chrétien M., Seidah N. G. 7B2 is a specific intracellular binding protein of the prohormone convertase PC2. J Neurochem. 1995 May;64(5):2303–2311. doi: 10.1046/j.1471-4159.1995.64052303.x. [DOI] [PubMed] [Google Scholar]
  10. Bosch V., Pawlita M. Mutational analysis of the human immunodeficiency virus type 1 env gene product proteolytic cleavage site. J Virol. 1990 May;64(5):2337–2344. doi: 10.1128/jvi.64.5.2337-2344.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Callebaut C., Krust B., Jacotot E., Hovanessian A. G. T cell activation antigen, CD26, as a cofactor for entry of HIV in CD4+ cells. Science. 1993 Dec 24;262(5142):2045–2050. doi: 10.1126/science.7903479. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. De Bie I., Savaria D., Roebroek A. J., Day R., Lazure C., Van de Ven W. J., Seidah N. G. Processing specificity and biosynthesis of the Drosophila melanogaster convertases dfurin1, dfurin1-CRR, dfurin1-X, and dfurin2. J Biol Chem. 1995 Jan 20;270(3):1020–1028. doi: 10.1074/jbc.270.3.1020. [DOI] [PubMed] [Google Scholar]
  14. Decroly E., Vandenbranden M., Ruysschaert J. M., Cogniaux J., Jacob G. S., Howard S. C., Marshall G., Kompelli A., Basak A., Jean F. The convertases furin and PC1 can both cleave the human immunodeficiency virus (HIV)-1 envelope glycoprotein gp160 into gp120 (HIV-1 SU) and gp41 (HIV-I TM). J Biol Chem. 1994 Apr 22;269(16):12240–12247. [PubMed] [Google Scholar]
  15. Dupuy A., Lindberg I., Zhou Y., Akil H., Lazure C., Chrétien M., Seidah N. G., Day R. Processing of prodynorphin by the prohormone convertase PC1 results in high molecular weight intermediate forms. Cleavage at a single arginine residue. FEBS Lett. 1994 Jan 3;337(1):60–65. doi: 10.1016/0014-5793(94)80630-6. [DOI] [PubMed] [Google Scholar]
  16. Elbein A. D. Inhibitors of the biosynthesis and processing of N-linked oligosaccharide chains. Annu Rev Biochem. 1987;56:497–534. doi: 10.1146/annurev.bi.56.070187.002433. [DOI] [PubMed] [Google Scholar]
  17. Freed E. O., Myers D. J., Risser R. Identification of the principal neutralizing determinant of human immunodeficiency virus type 1 as a fusion domain. J Virol. 1991 Jan;65(1):190–194. doi: 10.1128/jvi.65.1.190-194.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Freed E. O., Myers D. J., Risser R. Mutational analysis of the cleavage sequence of the human immunodeficiency virus type 1 envelope glycoprotein precursor gp160. J Virol. 1989 Nov;63(11):4670–4675. doi: 10.1128/jvi.63.11.4670-4675.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Geyer H., Holschbach C., Hunsmann G., Schneider J. Carbohydrates of human immunodeficiency virus. Structures of oligosaccharides linked to the envelope glycoprotein 120. J Biol Chem. 1988 Aug 25;263(24):11760–11767. [PubMed] [Google Scholar]
  20. Gruters R. A., Neefjes J. J., Tersmette M., de Goede R. E., Tulp A., Huisman H. G., Miedema F., Ploegh H. L. Interference with HIV-induced syncytium formation and viral infectivity by inhibitors of trimming glucosidase. Nature. 1987 Nov 5;330(6143):74–77. doi: 10.1038/330074a0. [DOI] [PubMed] [Google Scholar]
  21. Gu M., Rappaport J., Leppla S. H. Furin is important but not essential for the proteolytic maturation of gp160 of HIV-1. FEBS Lett. 1995 May 22;365(1):95–97. doi: 10.1016/0014-5793(95)00447-h. [DOI] [PubMed] [Google Scholar]
  22. Guo H. G., Veronese F. M., Tschachler E., Pal R., Kalyanaraman V. S., Gallo R. C., Reitz M. S., Jr Characterization of an HIV-1 point mutant blocked in envelope glycoprotein cleavage. Virology. 1990 Jan;174(1):217–224. doi: 10.1016/0042-6822(90)90070-8. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. 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]
  25. Horimoto T., Nakayama K., Smeekens S. P., Kawaoka Y. Proprotein-processing endoproteases PC6 and furin both activate hemagglutinin of virulent avian influenza viruses. J Virol. 1994 Sep;68(9):6074–6078. doi: 10.1128/jvi.68.9.6074-6078.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. Ivanoff L. A., Dubay J. W., Morris J. F., Roberts S. J., Gutshall L., Sternberg E. J., Hunter E., Matthews T. J., Petteway S. R., Jr V3 loop region of the HIV-1 gp120 envelope protein is essential for virus infectivity. Virology. 1992 Apr;187(2):423–432. doi: 10.1016/0042-6822(92)90444-t. [DOI] [PubMed] [Google Scholar]
  28. Jean F., Basak A., Rondeau N., Benjannet S., Hendy G. N., Seidah N. G., Chrétien M., Lazure C. Enzymic characterization of murine and human prohormone convertase-1 (mPC1 and hPC1) expressed in mammalian GH4C1 cells. Biochem J. 1993 Jun 15;292(Pt 3):891–900. doi: 10.1042/bj2920891. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Johnson R. C., Darlington D. N., Hand T. A., Bloomquist B. T., Mains R. E. PACE4: a subtilisin-like endoprotease prevalent in the anterior pituitary and regulated by thyroid status. Endocrinology. 1994 Sep;135(3):1178–1185. doi: 10.1210/endo.135.3.8070361. [DOI] [PubMed] [Google Scholar]
  30. Karlsson G. B., Butters T. D., Dwek R. A., Platt F. M. Effects of the imino sugar N-butyldeoxynojirimycin on the N-glycosylation of recombinant gp120. J Biol Chem. 1993 Jan 5;268(1):570–576. [PubMed] [Google Scholar]
  31. Kido H., Kamoshita K., Fukutomi A., Katunuma N. Processing protease for gp160 human immunodeficiency virus type I envelope glycoprotein precursor in human T4+ lymphocytes. Purification and characterization. J Biol Chem. 1993 Jun 25;268(18):13406–13413. [PubMed] [Google Scholar]
  32. Klausner R. D., Donaldson J. G., Lippincott-Schwartz J. Brefeldin A: insights into the control of membrane traffic and organelle structure. J Cell Biol. 1992 Mar;116(5):1071–1080. doi: 10.1083/jcb.116.5.1071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Klenk H. D., Garten W., Rott R. Inhibition of proteolytic cleavage of the hemagglutinin of influenza virus by the calcium-specific ionophore A23187. EMBO J. 1984 Dec 1;3(12):2911–2915. doi: 10.1002/j.1460-2075.1984.tb02231.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Klimpel K. R., Molloy S. S., Thomas G., Leppla S. H. Anthrax toxin protective antigen is activated by a cell surface protease with the sequence specificity and catalytic properties of furin. Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10277–10281. doi: 10.1073/pnas.89.21.10277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Kowalski M., Potz J., Basiripour L., Dorfman T., Goh W. C., Terwilliger E., Dayton A., Rosen C., Haseltine W., Sodroski J. Functional regions of the envelope glycoprotein of human immunodeficiency virus type 1. Science. 1987 Sep 11;237(4820):1351–1355. doi: 10.1126/science.3629244. [DOI] [PubMed] [Google Scholar]
  36. 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]
  37. Levy J. A. Pathogenesis of human immunodeficiency virus infection. Microbiol Rev. 1993 Mar;57(1):183–289. doi: 10.1128/mr.57.1.183-289.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Matlin K. S., Simons K. Reduced temperature prevents transfer of a membrane glycoprotein to the cell surface but does not prevent terminal glycosylation. Cell. 1983 Aug;34(1):233–243. doi: 10.1016/0092-8674(83)90154-x. [DOI] [PubMed] [Google Scholar]
  39. Matthews D. J., Goodman L. J., Gorman C. M., Wells J. A. A survey of furin substrate specificity using substrate phage display. Protein Sci. 1994 Aug;3(8):1197–1205. doi: 10.1002/pro.5560030805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Molloy S. S., Thomas L., VanSlyke J. K., Stenberg P. E., Thomas G. Intracellular trafficking and activation of the furin proprotein convertase: localization to the TGN and recycling from the cell surface. EMBO J. 1994 Jan 1;13(1):18–33. doi: 10.1002/j.1460-2075.1994.tb06231.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Morikawa Y., Barsov E., Jones I. Legitimate and illegitimate cleavage of human immunodeficiency virus glycoproteins by furin. J Virol. 1993 Jun;67(6):3601–3604. doi: 10.1128/jvi.67.6.3601-3604.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Moulard M., Montagnier L., Bahraoui E. Effects of calcium ions on proteolytic processing of HIV-1 gp160 precursor and on cell fusion. FEBS Lett. 1994 Feb 7;338(3):281–284. doi: 10.1016/0014-5793(94)80284-x. [DOI] [PubMed] [Google Scholar]
  43. Nakagawa T., Murakami K., Nakayama K. Identification of an isoform with an extremely large Cys-rich region of PC6, a Kex2-like processing endoprotease. FEBS Lett. 1993 Jul 26;327(2):165–171. doi: 10.1016/0014-5793(93)80163-o. [DOI] [PubMed] [Google Scholar]
  44. Nakayama K., Watanabe T., Nakagawa T., Kim W. S., Nagahama M., Hosaka M., Hatsuzawa K., Kondoh-Hashiba K., Murakami K. Consensus sequence for precursor processing at mono-arginyl sites. Evidence for the involvement of a Kex2-like endoprotease in precursor cleavages at both dibasic and mono-arginyl sites. J Biol Chem. 1992 Aug 15;267(23):16335–16340. [PubMed] [Google Scholar]
  45. Ohnishi Y., Shioda T., Nakayama K., Iwata S., Gotoh B., Hamaguchi M., Nagai Y. A furin-defective cell line is able to process correctly the gp160 of human immunodeficiency virus type 1. J Virol. 1994 Jun;68(6):4075–4079. doi: 10.1128/jvi.68.6.4075-4079.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Owens R. J., Compans R. W. The human immunodeficiency virus type 1 envelope glycoprotein precursor acquires aberrant intermolecular disulfide bonds that may prevent normal proteolytic processing. Virology. 1990 Dec;179(2):827–833. doi: 10.1016/0042-6822(90)90151-g. [DOI] [PubMed] [Google Scholar]
  47. Pal R., Hoke G. M., Sarngadharan M. G. Role of oligosaccharides in the processing and maturation of envelope glycoproteins of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1989 May;86(9):3384–3388. doi: 10.1073/pnas.86.9.3384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Paquet L., Bergeron F., Boudreault A., Seidah N. G., Chrétien M., Mbikay M., Lazure C. The neuroendocrine precursor 7B2 is a sulfated protein proteolytically processed by a ubiquitous furin-like convertase. J Biol Chem. 1994 Jul 29;269(30):19279–19285. [PubMed] [Google Scholar]
  49. Ratner L., Haseltine W., Patarca R., Livak K. J., Starcich B., Josephs S. F., Doran E. R., Rafalski J. A., Whitehorn E. A., Baumeister K. Complete nucleotide sequence of the AIDS virus, HTLV-III. Nature. 1985 Jan 24;313(6000):277–284. doi: 10.1038/313277a0. [DOI] [PubMed] [Google Scholar]
  50. 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]
  51. Sattentau Q. J., Moore J. P. Conformational changes induced in the human immunodeficiency virus envelope glycoprotein by soluble CD4 binding. J Exp Med. 1991 Aug 1;174(2):407–415. doi: 10.1084/jem.174.2.407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Seidah N. G., Chrétien M., Day R. The family of subtilisin/kexin like pro-protein and pro-hormone convertases: divergent or shared functions. Biochimie. 1994;76(3-4):197–209. doi: 10.1016/0300-9084(94)90147-3. [DOI] [PubMed] [Google Scholar]
  53. Seidah N. G., Day R., Marcinkiewicz M., Benjannet S., Chrétien M. Mammalian neural and endocrine pro-protein and pro-hormone convertases belonging to the subtilisin family of serine proteinases. Enzyme. 1991;45(5-6):271–284. doi: 10.1159/000468901. [DOI] [PubMed] [Google Scholar]
  54. Shilatifard A., Merkle R. K., Helland D. E., Welles J. L., Haseltine W. A., Cummings R. D. Complex-type N-linked oligosaccharides of gp120 from human immunodeficiency virus type 1 contain sulfated N-acetylglucosamine. J Virol. 1993 Feb;67(2):943–952. doi: 10.1128/jvi.67.2.943-952.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Stein B. S., Engleman E. G. Intracellular processing of the gp160 HIV-1 envelope precursor. Endoproteolytic cleavage occurs in a cis or medial compartment of the Golgi complex. J Biol Chem. 1990 Feb 15;265(5):2640–2649. [PubMed] [Google Scholar]
  56. Steiner D. F., Smeekens S. P., Ohagi S., Chan S. J. The new enzymology of precursor processing endoproteases. J Biol Chem. 1992 Nov 25;267(33):23435–23438. [PubMed] [Google Scholar]
  57. Syu W. J., Huang J. H., Essex M., Lee T. H. The N-terminal region of the human immunodeficiency virus envelope glycoprotein gp120 contains potential binding sites for CD4. Proc Natl Acad Sci U S A. 1990 May;87(10):3695–3699. doi: 10.1073/pnas.87.10.3695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Takahashi S., Hatsuzawa K., Watanabe T., Murakami K., Nakayama K. Sequence requirements for endoproteolytic processing of precursor proteins by furin: transfection and in vitro experiments. J Biochem. 1994 Jul;116(1):47–52. doi: 10.1093/oxfordjournals.jbchem.a124501. [DOI] [PubMed] [Google Scholar]
  59. Takahashi S., Kasai K., Hatsuzawa K., Kitamura N., Misumi Y., Ikehara Y., Murakami K., Nakayama K. A mutation of furin causes the lack of precursor-processing activity in human colon carcinoma LoVo cells. Biochem Biophys Res Commun. 1993 Sep 15;195(2):1019–1026. doi: 10.1006/bbrc.1993.2146. [DOI] [PubMed] [Google Scholar]
  60. Tsuneoka M., Nakayama K., Hatsuzawa K., Komada M., Kitamura N., Mekada E. Evidence for involvement of furin in cleavage and activation of diphtheria toxin. J Biol Chem. 1993 Dec 15;268(35):26461–26465. [PubMed] [Google Scholar]
  61. Van de Ven W. J., Roebroek A. J., Van Duijnhoven H. L. Structure and function of eukaryotic proprotein processing enzymes of the subtilisin family of serine proteases. Crit Rev Oncog. 1993;4(2):115–136. [PubMed] [Google Scholar]
  62. Walker B. D., Kowalski M., Goh W. C., Kozarsky K., Krieger M., Rosen C., Rohrschneider L., Haseltine W. A., Sodroski J. Inhibition of human immunodeficiency virus syncytium formation and virus replication by castanospermine. Proc Natl Acad Sci U S A. 1987 Nov;84(22):8120–8124. doi: 10.1073/pnas.84.22.8120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Willey R. L., Bonifacino J. S., Potts B. J., Martin M. A., Klausner R. D. Biosynthesis, cleavage, and degradation of the human immunodeficiency virus 1 envelope glycoprotein gp160. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9580–9584. doi: 10.1073/pnas.85.24.9580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. 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]
  65. Yahi N., Fantini J., Baghdiguian S., Mabrouk K., Tamalet C., Rochat H., Van Rietschoten J., Sabatier J. M. SPC3, a synthetic peptide derived from the V3 domain of human immunodeficiency virus type 1 (HIV-1) gp120, inhibits HIV-1 entry into CD4+ and CD4- cells by two distinct mechanisms. Proc Natl Acad Sci U S A. 1995 May 23;92(11):4867–4871. doi: 10.1073/pnas.92.11.4867. [DOI] [PMC free article] [PubMed] [Google Scholar]

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