Angiogenic and HIV-inhibitory functions of KSHV-encoded chemokines

Science

Volumn 278, Issue 5336, 1997, Pages 290-294

  Boshoff, Chris ^a   Endo, Yoshio ^b   Collins, Paul D ^c   Takeuchi, Yasuhiro ^a   Reeves, Jacqueline D ^a   Schweickart, Vicki L ^d   Siani, Michael A ^e   Sasaki, Takuma ^b   Williams, Timothy J ^c   Gray, Patrick W ^d   Moore, Patrick S ^f   Chang, Yuan ^f   Weiss, Robin A ^a  

^a INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^b KANAZAWA UNIVERSITY   (Japan)

^c NATIONAL HEART AND LUNG INSTITUTE   (United Kingdom)

^d ELI LILLY AND COMPANY   (United States)

^e Gryphon Therapeutics   (United States)

^f Columbia University ^*  (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD4 ANTIGEN; CHEMOKINE; CHEMOKINE RECEPTOR;

ANGIOGENESIS; ANTIVIRAL ACTIVITY; ARTICLE; EOSINOPHIL; HERPES VIRUS; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; KAPOSI SARCOMA; NONHUMAN; PRIORITY JOURNAL;

ANIMALS; CD4-POSITIVE T-LYMPHOCYTES; CHEMOKINES; CHEMOTAXIS, LEUKOCYTE; CHICK EMBRYO; EOSINOPHILS; HERPESVIRUS 8, HUMAN; HIV-1; HUMANS; LEUKOCYTES, MONONUCLEAR; MACROPHAGE INFLAMMATORY PROTEINS; NEOVASCULARIZATION, PATHOLOGIC; NEUTROPHILS; RECEPTORS, CHEMOKINE; RECEPTORS, CYTOKINE; RECEPTORS, HIV; TUMOR CELLS, CULTURED; VIRAL PROTEINS; VIRUS REPLICATION;

EID: 0030771974     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.278.5336.290     Document Type: Article

References (66)

1. V. Beral, in Cancer, HIV and AIDS, V. Beral, H. W. Jaffe, R. A. Weiss, Eds. (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 1991), vol. 10, pp. 5-22; A. Wahman, S. L. Melnick, F. S. Rhame, J. D. Potter, Epidemiol. Rev. 13, 178 (1991).
2. V. Beral, in Cancer, HIV and AIDS, V. Beral, H. W. Jaffe, R. A. Weiss, Eds. (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 1991), vol. 10, pp. 5-22; A. Wahman, S. L. Melnick, F. S. Rhame, J. D. Potter, Epidemiol. Rev. 13, 178 (1991).
3. B. Ensoli, G. Barillari, S. Z. Salahuddin, R. C. Gallo, S. F. Wong, Nature 345, 84 (1990); B. Ensoli et al., ibid. 371, 674 (1994); A. Albini et al., Nature Med. 2, 1371 (1996).
4. B. Ensoli, G. Barillari, S. Z. Salahuddin, R. C. Gallo, S. F. Wong, Nature 345, 84 (1990); B. Ensoli et al., ibid. 371, 674 (1994); A. Albini et al., Nature Med. 2, 1371 (1996).
5. B. Ensoli, G. Barillari, S. Z. Salahuddin, R. C. Gallo, S. F. Wong, Nature 345, 84 (1990); B. Ensoli et al., ibid. 371, 674 (1994); A. Albini et al., Nature Med. 2, 1371 (1996).
6. Y. Chang et al., Science 266, 1865 (1994); C. Boshoff et al., Lancet 345, 761 (1995); D. H. Kedes et al., Nature Med. 2, 918 (1996); S. J. Gao et al., ibid., p. 925; E. T. Lennette et al., Lancet 348, 858 (1996); G. R. Simpson et al., ibid., p. 1133.
7. Y. Chang et al., Science 266, 1865 (1994); C. Boshoff et al., Lancet 345, 761 (1995); D. H. Kedes et al., Nature Med. 2, 918 (1996); S. J. Gao et al., ibid., p. 925; E. T. Lennette et al., Lancet 348, 858 (1996); G. R. Simpson et al., ibid., p. 1133.
8. Y. Chang et al., Science 266, 1865 (1994); C. Boshoff et al., Lancet 345, 761 (1995); D. H. Kedes et al., Nature Med. 2, 918 (1996); S. J. Gao et al., ibid., p. 925; E. T. Lennette et al., Lancet 348, 858 (1996); G. R. Simpson et al., ibid., p. 1133.
9. Y. Chang et al., Science 266, 1865 (1994); C. Boshoff et al., Lancet 345, 761 (1995); D. H. Kedes et al., Nature Med. 2, 918 (1996); S. J. Gao et al., ibid., p. 925; E. T. Lennette et al., Lancet 348, 858 (1996); G. R. Simpson et al., ibid., p. 1133.
10. Y. Chang et al., Science 266, 1865 (1994); C. Boshoff et al., Lancet 345, 761 (1995); D. H. Kedes et al., Nature Med. 2, 918 (1996); S. J. Gao et al., ibid., p. 925; E. T. Lennette et al., Lancet 348, 858 (1996); G. R. Simpson et al., ibid., p. 1133.
11. Y. Chang et al., Science 266, 1865 (1994); C. Boshoff et al., Lancet 345, 761 (1995); D. H. Kedes et al., Nature Med. 2, 918 (1996); S. J. Gao et al., ibid., p. 925; E. T. Lennette et al., Lancet 348, 858 (1996); G. R. Simpson et al., ibid., p. 1133.
12. V. Beral, T. A. Peterman, R. L. Berkelman, H. W. Jaffe, Lancet 335, 123 (1990).
13. C. Boshoff et al., Nature Med. 1, 1274 (1995); K. A. Staskus et al., J. Virol. 71, 715 (1997).
14. C. Boshoff et al., Nature Med. 1, 1274 (1995); K. A. Staskus et al., J. Virol. 71, 715 (1997).
15. J. M. Orenstein et al., J. Acquired Immun. Defic. Syndr. 11, 735 (1997).
16. Although only the minority of cells in KS lesions at a specific time point undergo lytic replication [K. A. Staskus et al., J. Virol. 71, 715 (1997)], the demonstration that hundreds of virions are produced in such cells (6) indicates that high local levels of lytic KSHV-encoded proteins are produced in KS lesions. Our analysis by reverse transcriptase - polymerase chain reaction showed expression of vMIP-I and vMIP-II mRNA in KS biopsies (30).
17. J. Soulier et al., Blood 86, 1276 (1995); N. Dupin et al., N. Engl. J. Med. 333, 798 (1996); A. Gessain et al., Blood 87, 414 (1996); A. Chadburn et al., Cancer 80, 788 (1997); C. Parravicini et al., Am. J. Pathol., in press.
18. J. Soulier et al., Blood 86, 1276 (1995); N. Dupin et al., N. Engl. J. Med. 333, 798 (1996); A. Gessain et al., Blood 87, 414 (1996); A. Chadburn et al., Cancer 80, 788 (1997); C. Parravicini et al., Am. J. Pathol., in press.
19. J. Soulier et al., Blood 86, 1276 (1995); N. Dupin et al., N. Engl. J. Med. 333, 798 (1996); A. Gessain et al., Blood 87, 414 (1996); A. Chadburn et al., Cancer 80, 788 (1997); C. Parravicini et al., Am. J. Pathol., in press.
20. J. Soulier et al., Blood 86, 1276 (1995); N. Dupin et al., N. Engl. J. Med. 333, 798 (1996); A. Gessain et al., Blood 87, 414 (1996); A. Chadburn et al., Cancer 80, 788 (1997); C. Parravicini et al., Am. J. Pathol., in press.
21. J. Soulier et al., Blood 86, 1276 (1995); N. Dupin et al., N. Engl. J. Med. 333, 798 (1996); A. Gessain et al., Blood 87, 414 (1996); A. Chadburn et al., Cancer 80, 788 (1997); C. Parravicini et al., Am. J. Pathol., in press.
22. J. J. Russo et al., Proc. Natl. Acad. Sci. U.S.A. 93, 14862 (1996).
23. P. S. Moore, C. Boshoff, R. A. Weiss, Y. Chang, Science 274, 1739 (1996).
24. F. Neipel, J.-C. Albrecht, B. Fleckenstein, J. Virol. 71, 4187 (1997).
25. C. R. Mackay, J. Exp. Med. 184, 799 (1996); D. H. Adams, A. R. Lloyd, Lancet 349, 490 (1997).
26. C. R. Mackay, J. Exp. Med. 184, 799 (1996); D. H. Adams, A. R. Lloyd, Lancet 349, 490 (1997).
27. F. Cocchi et al., Science 270, 1811 (1995); T. Dragic et al., Nature 381, 667 (1996); H. Deng et al., ibid., p. 661; G. Alkhatib et al., Science 272, 1955 (1996); H. Choe et al., Cell 85, 1135 (1996); P. M. Murphy, Nature 385, 296 (1997).
28. F. Cocchi et al., Science 270, 1811 (1995); T. Dragic et al., Nature 381, 667 (1996); H. Deng et al., ibid., p. 661; G. Alkhatib et al., Science 272, 1955 (1996); H. Choe et al., Cell 85, 1135 (1996); P. M. Murphy, Nature 385, 296 (1997).
29. F. Cocchi et al., Science 270, 1811 (1995); T. Dragic et al., Nature 381, 667 (1996); H. Deng et al., ibid., p. 661; G. Alkhatib et al., Science 272, 1955 (1996); H. Choe et al., Cell 85, 1135 (1996); P. M. Murphy, Nature 385, 296 (1997).
30. F. Cocchi et al., Science 270, 1811 (1995); T. Dragic et al., Nature 381, 667 (1996); H. Deng et al., ibid., p. 661; G. Alkhatib et al., Science 272, 1955 (1996); H. Choe et al., Cell 85, 1135 (1996); P. M. Murphy, Nature 385, 296 (1997).
31. F. Cocchi et al., Science 270, 1811 (1995); T. Dragic et al., Nature 381, 667 (1996); H. Deng et al., ibid., p. 661; G. Alkhatib et al., Science 272, 1955 (1996); H. Choe et al., Cell 85, 1135 (1996); P. M. Murphy, Nature 385, 296 (1997).
32. F. Cocchi et al., Science 270, 1811 (1995); T. Dragic et al., Nature 381, 667 (1996); H. Deng et al., ibid., p. 661; G. Alkhatib et al., Science 272, 1955 (1996); H. Choe et al., Cell 85, 1135 (1996); P. M. Murphy, Nature 385, 296 (1997).
33. Synthetic chemokines were generated by native chemical ligation of peptides synthesized by solid-phase methods on an Applied Biosystems 430A Peptide Synthesizer [P. E. Dawson, T. W. Muir, I. Clark-Lewis, S. B. H. Kent, Science 266, 776 (1994)]. The resulting chemokines were purified by reversed-phase high-performance liquid chromatography and characterized by electrospray mass spectrometry. The purified synthetic chemokines were reconstituted in phosphate-buffered saline (PBS), and samples were frozen at -70°C. Chemokine sequences correspond to amino acid residues 25 to 29 for vMIP-1 and 21 to 94 for vMIP-II (Gen-Bank accession number U75698).
34. 4 cells per well overnight. The cells were then treated for 30 min at 37°C with appropriate concentrations of chemokine in 75 μl. One hundred FFUs of each virus in 75 μl were added and incubated for 3 hours at 37°C. The cells were then washed three times, and 500 μl of medium containing the appropriate chemokine at the correct concentration was added. After 5 days the cells were fixed for 10 min in cold acetone:methanol (1:1) and immunostained for in situ p24 as described [Á. McKnight, P. R. Clapham, R. A. Weiss, Virology 201, 8 (1994)]. Standard errors were estimated from duplicate wells, and the results (Fig. 1) are representative of three separate experiments.
35. 4 cells per well overnight. The cells were then treated for 30 min at 37°C with appropriate concentrations of chemokine in 75 μl. One hundred FFUs of each virus in 75 μl were added and incubated for 3 hours at 37°C. The cells were then washed three times, and 500 μl of medium containing the appropriate chemokine at the correct concentration was added. After 5 days the cells were fixed for 10 min in cold acetone:methanol (1:1) and immunostained for in situ p24 as described [Á. McKnight, P. R. Clapham, R. A. Weiss, Virology 201, 8 (1994)]. Standard errors were estimated from duplicate wells, and the results (Fig. 1) are representative of three separate experiments.
36. 4 cells per well overnight. The cells were then treated for 30 min at 37°C with appropriate concentrations of chemokine in 75 μl. One hundred FFUs of each virus in 75 μl were added and incubated for 3 hours at 37°C. The cells were then washed three times, and 500 μl of medium containing the appropriate chemokine at the correct concentration was added. After 5 days the cells were fixed for 10 min in cold acetone:methanol (1:1) and immunostained for in situ p24 as described [Á. McKnight, P. R. Clapham, R. A. Weiss, Virology 201, 8 (1994)]. Standard errors were estimated from duplicate wells, and the results (Fig. 1) are representative of three separate experiments.
37. M. J. Endres et al., Cell 87, 745 (1996); J. D. Reeves et al., Virology 231, 130 (1997).
38. M. J. Endres et al., Cell 87, 745 (1996); J. D. Reeves et al., Virology 231, 130 (1997).
39. Neither RANTES, vMIP-I, nor vMIP-II had appreciable effect on SF162 infection of U87/CD4 CCR5 cells, whereas vMIP-II and vMIP-I blocked infection by SL-2 at 400 nM by more than 50 and 25%, respectively. vMIP-II, but not vMIP-I, blocked the SI strains 89.6 and 2028 at 200 nM by 50 and 20%, respectively, compared with RANTES, which blocked infection of these viruses completely at 100 nM. On U87/CD4 CXCR4 cells, both vMIP-I and vMIP-II showed little activity (10 to 30% inhibition at 200 nM) in blocking infection by strain 89.6 or 2028. On U87 CXCR4 cells (CD4 negative), inhibition of infection by HIV-2 ROD/B was ∼50% at 200 nM by vMIP-I and vMIP-II.
40. P. D. Ponath et al., J. Exp. Med. 183, 2437 (1996); B. L. Daugherty et al., ibid., p. 2349.
41. P. D. Ponath et al., J. Exp. Med. 183, 2437 (1996); B. L. Daugherty et al., ibid., p. 2349.
42. 2+ at 37°C of 224 nM. In experiments designed to investigate desensitization between agonists, the first agonist (the desensitizing agonist) was added after 50 s and the second agonist added 150 s later.
43. A. E. I. Proudfoot et al., J. Biol. Chem. 271, 2599 (1996); B. Moser et al., ibid. 268, 7125 (1993).
44. A. E. I. Proudfoot et al., J. Biol. Chem. 271, 2599 (1996); B. Moser et al., ibid. 268, 7125 (1993).
45. K. Neote, D. DiGregorio, J. Y. Mak, R. Horuk, T. J. Schall, Cell 72, 415 (1993); J. L. Gao et al., J. Exp. Med. 177, 1421 (1993).
46. K. Neote, D. DiGregorio, J. Y. Mak, R. Horuk, T. J. Schall, Cell 72, 415 (1993); J. L. Gao et al., J. Exp. Med. 177, 1421 (1993).
47. 2), eosinophils migrating through the transwell were counted on a FACScan flow cytometer (Becton Dickinson).
48. W. Risau, Nature 387, 671 (1997).
49. A. L. Angiolillo, C. Sgadari, G. Tosato, Ann. N.Y. Acad. Sci. 795, 158 (1996); R. M. Strieter et al., J. Biol. Chem. 270, 27348 (1995); Y. Cao, C. Chen, J. A. Weatherbee, M. Tsang, J. Folkman, J. Exp. Med. 182, 2069 (1995).
50. A. L. Angiolillo, C. Sgadari, G. Tosato, Ann. N.Y. Acad. Sci. 795, 158 (1996); R. M. Strieter et al., J. Biol. Chem. 270, 27348 (1995); Y. Cao, C. Chen, J. A. Weatherbee, M. Tsang, J. Folkman, J. Exp. Med. 182, 2069 (1995).
51. A. L. Angiolillo, C. Sgadari, G. Tosato, Ann. N.Y. Acad. Sci. 795, 158 (1996); R. M. Strieter et al., J. Biol. Chem. 270, 27348 (1995); Y. Cao, C. Chen, J. A. Weatherbee, M. Tsang, J. Folkman, J. Exp. Med. 182, 2069 (1995).
52. D. Knighton, D. Ausprunk, D. Tapper, J. Folkman, Br. J. Cancer 35, 347 (1977); P. C. Brooks, R. A. F. Clark, D. A. Cheresh, Science 264, 569 (1994); M. Friedlander et al., ibid. 270, 1500 (1995).
53. D. Knighton, D. Ausprunk, D. Tapper, J. Folkman, Br. J. Cancer 35, 347 (1977); P. C. Brooks, R. A. F. Clark, D. A. Cheresh, Science 264, 569 (1994); M. Friedlander et al., ibid. 270, 1500 (1995).
54. D. Knighton, D. Ausprunk, D. Tapper, J. Folkman, Br. J. Cancer 35, 347 (1977); P. C. Brooks, R. A. F. Clark, D. A. Cheresh, Science 264, 569 (1994); M. Friedlander et al., ibid. 270, 1500 (1995).
55. Angiogenic activities of synthetically prepared viral and human chemokines were evaluated by the chick CAM assay as described [T. Oikawa et al., Cancer Lett. 59, 57 (1991)]. Fertilized Plymouth Rock × White Leghorn eggs were incubated at 37°C in a humidified atmosphere (relative humidity, ∼70%). Test samples were dissolved in sterile distilled water or PBS. Sterilized sample solution was mixed with an equal volume of autoclaved 2% methylcellulose. Controls were prepared with vehicle only (1% methylcellulose solution). The sample solution (20 μl) was dropped on Parafilm and dried up. The methylcellulose disks were stripped off from the Parafilm and placed on a CAM of 10-or 11-day-old chick embryos. After 3 days, the CAMs were observed by means of an Olympus stereoscope. A 20% fat emulsion (Intralipos 20%, Midori-Juji, Osaka, Japan) was injected into the CAM to increase the contrast between blood and surrounding tissues [R. Danesi et al., Clin. Cancer Res. 3, 265 (1997)]. The CAMs were photographed for evaluation of angiogenic response. Angiogenic responses were graded independently by three investigators as negative, positive, or unclear on the basis of infiltration of blood vessels into the area of the implanted methylcellulose.
56. Angiogenic activities of synthetically prepared viral and human chemokines were evaluated by the chick CAM assay as described [T. Oikawa et al., Cancer Lett. 59, 57 (1991)]. Fertilized Plymouth Rock × White Leghorn eggs were incubated at 37°C in a humidified atmosphere (relative humidity, ∼70%). Test samples were dissolved in sterile distilled water or PBS. Sterilized sample solution was mixed with an equal volume of autoclaved 2% methylcellulose. Controls were prepared with vehicle only (1% methylcellulose solution). The sample solution (20 μl) was dropped on Parafilm and dried up. The methylcellulose disks were stripped off from the Parafilm and placed on a CAM of 10-or 11-day-old chick embryos. After 3 days, the CAMs were observed by means of an Olympus stereoscope. A 20% fat emulsion (Intralipos 20%, Midori-Juji, Osaka, Japan) was injected into the CAM to increase the contrast between blood and surrounding tissues [R. Danesi et al., Clin. Cancer Res. 3, 265 (1997)]. The CAMs were photographed for evaluation of angiogenic response. Angiogenic responses were graded independently by three investigators as negative, positive, or unclear on the basis of infiltration of blood vessels into the area of the implanted methylcellulose.
57. T. Kledal et al., Science 277, 1656 (1997).
58. J. He et al., Nature 385, 645 (1997).
59. S. A. Miles et al., Proc. Natl. Acad. Sci. U.S.A. 87, 4068 (1990); K. Yoshizaki et al., Blood 74, 1360 (1989); K. Weindel, D. Marme, H. A. Weich, Biochem. Biophys. Res. Commun. 183, 1167(1992); R. Masood et al., Proc. Natl. Acad. Sci. U.S.A. 94, 979 (1997).
60. S. A. Miles et al., Proc. Natl. Acad. Sci. U.S.A. 87, 4068 (1990); K. Yoshizaki et al., Blood 74, 1360 (1989); K. Weindel, D. Marme, H. A. Weich, Biochem. Biophys. Res. Commun. 183, 1167(1992); R. Masood et al., Proc. Natl. Acad. Sci. U.S.A. 94, 979 (1997).
61. S. A. Miles et al., Proc. Natl. Acad. Sci. U.S.A. 87, 4068 (1990); K. Yoshizaki et al., Blood 74, 1360 (1989); K. Weindel, D. Marme, H. A. Weich, Biochem. Biophys. Res. Commun. 183, 1167(1992); R. Masood et al., Proc. Natl. Acad. Sci. U.S.A. 94, 979 (1997).
62. S. A. Miles et al., Proc. Natl. Acad. Sci. U.S.A. 87, 4068 (1990); K. Yoshizaki et al., Blood 74, 1360 (1989); K. Weindel, D. Marme, H. A. Weich, Biochem. Biophys. Res. Commun. 183, 1167(1992); R. Masood et al., Proc. Natl. Acad. Sci. U.S.A. 94, 979 (1997).
63. C. Boshoff et al., unpublished data.
64. G. Simmons et al., J. Virol. 70, 8355 (1996).
65. P. J. Jose et al., J. Exp. Med. 179, 881 (1994).
66. We thank D. Littman and J Hoxie for providing U87/ CD4 cells, and P. Clapham and G. Simmons for doing HIV-1 experiments. Supported by the Cancer Research Campaign; the Medical Research Council; the Japanese Ministry of Health and Welfare; the Japanese Ministry of Education, Sciences, Sports and Culture; the Wellcome Trust; The National Asthma Campaign; and NCI (CA 67391).