Age-dependent diarrhea induced by a rotaviral nonstructural glycoprotein

Science

Volumn 272, Issue 5258, 1996, Pages 101-104

  Ball, Judith M ^a   Tian, Peng ^a   Zeng, Carl Q Y ^a   Morris, Andrew P ^b   Estes, Mary K ^a  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

^b UNIVERSITY OF TEXAS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHLORIDE ION; ENTEROTOXIN; RECEPTOR; VIRUS GLYCOPROTEIN;

AGE; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CHLORIDE TRANSPORT; CONTROLLED STUDY; DIARRHEA; DOSE RESPONSE; ELECTROPHYSIOLOGY; INTESTINE MUCOSA; MOUSE; NEWBORN; NONHUMAN; PRIORITY JOURNAL; ROTAVIRUS; SIGNAL TRANSDUCTION; VIRUS INFECTION;

EID: 0029972477     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.272.5258.101     Document Type: Article

References (51)

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6. D. Y. Graham, J. W Sackman, M. K. Estes, Dig. Dis. Sci. 29, 1028 (1984)
7. J Collins et al., J. Pediatr Gastroenterol. Nutr. 7, 264 (1988).
8. M. P. Osborne et al, ibid., p. 236.
9. K. W. Theil, E. Bohl, R Cross, E Kohler, A. Agnes, Am J. Vet. Res 39, 213 (1978), J. P McAdaragh et al., ibid 41, 1572 (1980); L. J. Saif, L. A Ward, L Yuan, B. I. Rosen, T. L To, in Proceedings of the Sapparo International Symposiums on Viral Gastroenteritis. S. Chiba, S. Nakata, M. K. Estes, Eds. (Arch. Virol., special issue, in press); C A Mebus, Am. J Dig. Dis. 21, 592 (1976).
10. K. W. Theil, E. Bohl, R Cross, E Kohler, A. Agnes, Am J. Vet. Res 39, 213 (1978), J. P McAdaragh et al., ibid 41, 1572 (1980); L. J. Saif, L. A Ward, L Yuan, B. I. Rosen, T. L To, in Proceedings of the Sapparo International Symposiums on Viral Gastroenteritis. S. Chiba, S. Nakata, M. K. Estes, Eds. (Arch. Virol., special issue, in press); C A Mebus, Am. J Dig. Dis. 21, 592 (1976).
11. K. W. Theil, E. Bohl, R Cross, E Kohler, A. Agnes, Am J. Vet. Res 39, 213 (1978), J. P McAdaragh et al., ibid 41, 1572 (1980); L. J. Saif, L. A Ward, L Yuan, B. I. Rosen, T. L To, in Proceedings of the Sapparo International Symposiums on Viral Gastroenteritis. S. Chiba, S. Nakata, M. K. Estes, Eds. (Arch. Virol., special issue, in press); C A Mebus, Am. J Dig. Dis. 21, 592 (1976).
12. K. W. Theil, E. Bohl, R Cross, E Kohler, A. Agnes, Am J. Vet. Res 39, 213 (1978), J. P McAdaragh et al., ibid 41, 1572 (1980); L. J. Saif, L. A Ward, L Yuan, B. I. Rosen, T. L To, in Proceedings of the Sapparo International Symposiums on Viral Gastroenteritis. S. Chiba, S. Nakata, M. K. Estes, Eds. (Arch. Virol., special issue, in press); C A Mebus, Am. J Dig. Dis. 21, 592 (1976).
13. To determine the presence of diarrhea, we examined each mouse pup every 1 to 2 hours for the first 8 hours and at 24 hours after inoculation by gently pressing the abdomen. Diarrhea was noted and scored from 1 to 4, with a score of 1 reflecting unusually loose yellow stool and a score of 4 indicating completely liquid stool A score of 2 (mucous with liquid stool, some loose but solid stool) and above was considered diarrhea A score of 1 was noted but was not considered as diarrhea. The scoring was done by a single person and the pups were coded during analysis of diarrhea. Other symptoms monitored included lethargy, coldness to the touch, and ruffled coats in older animals.
14. J. M Ball, P. Tian, C. Q -Y. Zeng, A. P. Morris, M. K. Estes, data not shown.
15. Synthetic peptides used in this study were originally selected on the basis of algorithms that predict surface potential [J. M. R. Parker, D. Quo, R S. Hodges, Biochemistry 25, 5425 (1986)], turn potential (Pt) [P Y Chou and G. D. Passman, Adv. Enzymol. 47, 45 (1978)], and amphipathic structure [H. Margoltt et al, J Immunol. 138, 2213 (1987)]. A block length of 11 was used and an amphipathic score (AS) of 4 was considered significant The NSP4 114-135 peptide has an AS of 35 All peptides were synthesized by the University of Pittsburgh Peptide Core Facility with the use of a 9-fluoroenyl methyloxycarbonyl chemical strategy and standard protocols [L A. Carpino and G H. Han, J. Org Chem 37, 5748 (1970)]. Coupling and deblocking efficiencies were monitored by the ninhydrin colorimetric reaction [E. Kaiser, R L. Colescott, C. D. Bosinger, P. I Cook, Anal. Biochem. 34, 595 (1970)]. Peptides were cleaved from their solid resin support and separated from organic contaminants by multiple cold ether extractions and conventional gel filtration chromatography (Sephadex G-25). The final peptide product was characterized by reversed-phase high-performance liquid chromatography (HPLC) (Deltapak C4, Waters) and plasma desorption mass spectroscopy [G P. Jonnson et al., Anal. Chem. 58, 1084 (1986)]. Only those peptides with the correct theoretical mass and 90% or greater full-length product were used in these studies. Peptides were purified either by HPLC on a semipreparative, reversed-phase C18 column (uBondapak, Waters) or by multiple elutions from a conventional gel filtration column (1.5 mm by 40 mm). Peptide purity and sterility were confirmed before inoculations.
16. Synthetic peptides used in this study were originally selected on the basis of algorithms that predict surface potential [J. M. R. Parker, D. Quo, R S. Hodges, Biochemistry 25, 5425 (1986)], turn potential (Pt) [P Y Chou and G. D. Passman, Adv. Enzymol. 47, 45 (1978)], and amphipathic structure [H. Margoltt et al, J Immunol. 138, 2213 (1987)]. A block length of 11 was used and an amphipathic score (AS) of 4 was considered significant The NSP4 114-135 peptide has an AS of 35 All peptides were synthesized by the University of Pittsburgh Peptide Core Facility with the use of a 9-fluoroenyl methyloxycarbonyl chemical strategy and standard protocols [L A. Carpino and G H. Han, J. Org Chem 37, 5748 (1970)]. Coupling and deblocking efficiencies were monitored by the ninhydrin colorimetric reaction [E. Kaiser, R L. Colescott, C. D. Bosinger, P. I Cook, Anal. Biochem. 34, 595 (1970)]. Peptides were cleaved from their solid resin support and separated from organic contaminants by multiple cold ether extractions and conventional gel filtration chromatography (Sephadex G-25). The final peptide product was characterized by reversed-phase high-performance liquid chromatography (HPLC) (Deltapak C4, Waters) and plasma desorption mass spectroscopy [G P. Jonnson et al., Anal. Chem. 58, 1084 (1986)]. Only those peptides with the correct theoretical mass and 90% or greater full-length product were used in these studies. Peptides were purified either by HPLC on a semipreparative, reversed-phase C18 column (uBondapak, Waters) or by multiple elutions from a conventional gel filtration column (1.5 mm by 40 mm). Peptide purity and sterility were confirmed before inoculations.
17. Synthetic peptides used in this study were originally selected on the basis of algorithms that predict surface potential [J. M. R. Parker, D. Quo, R S. Hodges, Biochemistry 25, 5425 (1986)], turn potential (Pt) [P Y Chou and G. D. Passman, Adv. Enzymol. 47, 45 (1978)], and amphipathic structure [H. Margoltt et al, J Immunol. 138, 2213 (1987)]. A block length of 11 was used and an amphipathic score (AS) of 4 was considered significant The NSP4 114-135 peptide has an AS of 35 All peptides were synthesized by the University of Pittsburgh Peptide Core Facility with the use of a 9-fluoroenyl methyloxycarbonyl chemical strategy and standard protocols [L A. Carpino and G H. Han, J. Org Chem 37, 5748 (1970)]. Coupling and deblocking efficiencies were monitored by the ninhydrin colorimetric reaction [E. Kaiser, R L. Colescott, C. D. Bosinger, P. I Cook, Anal. Biochem. 34, 595 (1970)]. Peptides were cleaved from their solid resin support and separated from organic contaminants by multiple cold ether extractions and conventional gel filtration chromatography (Sephadex G-25). The final peptide product was characterized by reversed-phase high-performance liquid chromatography (HPLC) (Deltapak C4, Waters) and plasma desorption mass spectroscopy [G P. Jonnson et al., Anal. Chem. 58, 1084 (1986)]. Only those peptides with the correct theoretical mass and 90% or greater full-length product were used in these studies. Peptides were purified either by HPLC on a semipreparative, reversed-phase C18 column (uBondapak, Waters) or by multiple elutions from a conventional gel filtration column (1.5 mm by 40 mm). Peptide purity and sterility were confirmed before inoculations.
18. Synthetic peptides used in this study were originally selected on the basis of algorithms that predict surface potential [J. M. R. Parker, D. Quo, R S. Hodges, Biochemistry 25, 5425 (1986)], turn potential (Pt) [P Y Chou and G. D. Passman, Adv. Enzymol. 47, 45 (1978)], and amphipathic structure [H. Margoltt et al, J Immunol. 138, 2213 (1987)]. A block length of 11 was used and an amphipathic score (AS) of 4 was considered significant The NSP4 114-135 peptide has an AS of 35 All peptides were synthesized by the University of Pittsburgh Peptide Core Facility with the use of a 9-fluoroenyl methyloxycarbonyl chemical strategy and standard protocols [L A. Carpino and G H. Han, J. Org Chem 37, 5748 (1970)]. Coupling and deblocking efficiencies were monitored by the ninhydrin colorimetric reaction [E. Kaiser, R L. Colescott, C. D. Bosinger, P. I Cook, Anal. Biochem. 34, 595 (1970)]. Peptides were cleaved from their solid resin support and separated from organic contaminants by multiple cold ether extractions and conventional gel filtration chromatography (Sephadex G-25). The final peptide product was characterized by reversed-phase high-performance liquid chromatography (HPLC) (Deltapak C4, Waters) and plasma desorption mass spectroscopy [G P. Jonnson et al., Anal. Chem. 58, 1084 (1986)]. Only those peptides with the correct theoretical mass and 90% or greater full-length product were used in these studies. Peptides were purified either by HPLC on a semipreparative, reversed-phase C18 column (uBondapak, Waters) or by multiple elutions from a conventional gel filtration column (1.5 mm by 40 mm). Peptide purity and sterility were confirmed before inoculations.
19. Synthetic peptides used in this study were originally selected on the basis of algorithms that predict surface potential [J. M. R. Parker, D. Quo, R S. Hodges, Biochemistry 25, 5425 (1986)], turn potential (Pt) [P Y Chou and G. D. Passman, Adv. Enzymol. 47, 45 (1978)], and amphipathic structure [H. Margoltt et al, J Immunol. 138, 2213 (1987)]. A block length of 11 was used and an amphipathic score (AS) of 4 was considered significant The NSP4 114-135 peptide has an AS of 35 All peptides were synthesized by the University of Pittsburgh Peptide Core Facility with the use of a 9-fluoroenyl methyloxycarbonyl chemical strategy and standard protocols [L A. Carpino and G H. Han, J. Org Chem 37, 5748 (1970)]. Coupling and deblocking efficiencies were monitored by the ninhydrin colorimetric reaction [E. Kaiser, R L. Colescott, C. D. Bosinger, P. I Cook, Anal. Biochem. 34, 595 (1970)]. Peptides were cleaved from their solid resin support and separated from organic contaminants by multiple cold ether extractions and conventional gel filtration chromatography (Sephadex G-25). The final peptide product was characterized by reversed-phase high-performance liquid chromatography (HPLC) (Deltapak C4, Waters) and plasma desorption mass spectroscopy [G P. Jonnson et al., Anal. Chem. 58, 1084 (1986)]. Only those peptides with the correct theoretical mass and 90% or greater full-length product were used in these studies. Peptides were purified either by HPLC on a semipreparative, reversed-phase C18 column (uBondapak, Waters) or by multiple elutions from a conventional gel filtration column (1.5 mm by 40 mm). Peptide purity and sterility were confirmed before inoculations.
20. Synthetic peptides used in this study were originally selected on the basis of algorithms that predict surface potential [J. M. R. Parker, D. Quo, R S. Hodges, Biochemistry 25, 5425 (1986)], turn potential (Pt) [P Y Chou and G. D. Passman, Adv. Enzymol. 47, 45 (1978)], and amphipathic structure [H. Margoltt et al, J Immunol. 138, 2213 (1987)]. A block length of 11 was used and an amphipathic score (AS) of 4 was considered significant The NSP4 114-135 peptide has an AS of 35 All peptides were synthesized by the University of Pittsburgh Peptide Core Facility with the use of a 9-fluoroenyl methyloxycarbonyl chemical strategy and standard protocols [L A. Carpino and G H. Han, J. Org Chem 37, 5748 (1970)]. Coupling and deblocking efficiencies were monitored by the ninhydrin colorimetric reaction [E. Kaiser, R L. Colescott, C. D. Bosinger, P. I Cook, Anal. Biochem. 34, 595 (1970)]. Peptides were cleaved from their solid resin support and separated from organic contaminants by multiple cold ether extractions and conventional gel filtration chromatography (Sephadex G-25). The final peptide product was characterized by reversed-phase high-performance liquid chromatography (HPLC) (Deltapak C4, Waters) and plasma desorption mass spectroscopy [G P. Jonnson et al., Anal. Chem. 58, 1084 (1986)]. Only those peptides with the correct theoretical mass and 90% or greater full-length product were used in these studies. Peptides were purified either by HPLC on a semipreparative, reversed-phase C18 column (uBondapak, Waters) or by multiple elutions from a conventional gel filtration column (1.5 mm by 40 mm). Peptide purity and sterility were confirmed before inoculations.
21. P Tian et al, J Virol 68, 251 (1994); P. Tian et al., ibid. 69, 5763 (1995).
22. P Tian et al, J Virol 68, 251 (1994); P. Tian et al., ibid. 69, 5763 (1995).
23. Peptide sequences used in this study include NSP4 114-135 [G. W. Both, L J. Siegman, R. R. Bellamy, P. H. Atkinson, ibid. 48, 335 (1983)], [DKLTT-REIEQVELLKRIYDKLT (25)], AS = 35; NSP4 2-22 [EKLTDLNYTLSVITLMNNTLH (25)], AS = 14; an extended highly amphipathic peptide, NSP4 90-123 [TKDEIEKQMDRVVKEMRRQLEMIDKLTTREIEQ (25)] AS = 71, a mutated peptide, mNSP4 131K [DKLTTREIEQVELLKRIKDKLT (25)] AS = 31; and a peptide from the Norwalk virus capsid protein [X Jiang, D. Y. Graham, P Madore, T. Tanaka, M. K Estes, Science 250, 1580 (1990)], NV 464-483 [DT-GRNLGEFKAYPDGFLTCV (25)], AS = 41
24. Peptide sequences used in this study include NSP4 114-135 [G. W. Both, L J. Siegman, R. R. Bellamy, P. H. Atkinson, ibid. 48, 335 (1983)], [DKLTT-REIEQVELLKRIYDKLT (25)], AS = 35; NSP4 2-22 [EKLTDLNYTLSVITLMNNTLH (25)], AS = 14; an extended highly amphipathic peptide, NSP4 90-123 [TKDEIEKQMDRVVKEMRRQLEMIDKLTTREIEQ (25)] AS = 71, a mutated peptide, mNSP4 131K [DKLTTREIEQVELLKRIKDKLT (25)] AS = 31; and a peptide from the Norwalk virus capsid protein [X Jiang, D. Y. Graham, P Madore, T. Tanaka, M. K Estes, Science 250, 1580 (1990)], NV 464-483 [DT-GRNLGEFKAYPDGFLTCV (25)], AS = 41
25. L. J. Reed and H. Muench, Am. J. Hyg. 27, 493 (1938).
26. NSP4 114-135 peptide-specific antiserum was generated in New Zealand white rabbits by immunization with peptide cross-linked via glutaraldehyde to the protein eamer keyhole limpet hemocyanin (25) The first inoculum was emulsified in Freund's complete adjuvant (Gibco); all subsequent inoculations were prepared in incomplete Freund's adjuvant. Rabbits were injected intramuscularly once in each hip and subcutaneously across the back of the neck. Boosting doses of emulsified antigen (100 nmol of peptide) were done every 4 weeks for a total of five immunizations Pre- and postimmunization sera were evaluated by peptide enzymelinked immunosorbent assays (ELISAs) (titer of 400 to 3200) as previously described (J M Ball, N L Henry, R. C. Montelaro, M. J. Newman, J Immunol Methods 171, 37 (1994)] and by protein immunoblot analyses.
27. J. M Ball and M K Estes, in preparation.
28. sc measurements were taken and intestinal mucosal sheets were challenged with peptide, Cch, or FSK. Bumetamide sensitivity was tested and confirmed the chloride secretory response
29. sc measurements were taken and intestinal mucosal sheets were challenged with peptide, Cch, or FSK. Bumetamide sensitivity was tested and confirmed the chloride secretory response
30. sc measurements were taken and intestinal mucosal sheets were challenged with peptide, Cch, or FSK. Bumetamide sensitivity was tested and confirmed the chloride secretory response
31. Using a newly established ELISA that is sensitive enough to detect 31.3 ng or 0.02 nmol of NSP4, we have detected NSP4 in the stools of mice with diarrhea at concentrations necessary to induce disease NSP4 was not present in stools from animals without diarrhea.
32. R. F. Ramig, Microb. Pathog. 4, 189 (1988).
33. R. L Ward, M. M. McNeal, J F Sheridan, J Virol. 64, 5070 (1990), N. Feng, H W. Bums, L. Bracy, H. B Greenberg, ibid 68, 7766 (1994); J. W. Burns, et al., Virology 207, 143 (1995).
34. R. L Ward, M. M. McNeal, J F Sheridan, J Virol. 64, 5070 (1990), N. Feng, H W. Bums, L. Bracy, H. B Greenberg, ibid 68, 7766 (1994); J. W. Burns, et al., Virology 207, 143 (1995).
35. R. L Ward, M. M. McNeal, J F Sheridan, J Virol. 64, 5070 (1990), N. Feng, H W. Bums, L. Bracy, H. B Greenberg, ibid 68, 7766 (1994); J. W. Burns, et al., Virology 207, 143 (1995).
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37. L. M. Little and J. A. Shadduck, Infect. Immun. 38, 755 (1982); W. G Starkey et al., J. Gen. Virol. 67, 2625 (1986).
38. Y. Hoshino et al., Virology 209, 274 (1995).
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41. M. N Burgess et al. Infect. Immunol. 221, 526 (1978); R. A Giannella, Annu. Rev. Med. 32, 341 (1981); W. J. Krause, R. H. Freeman, L R Forte, Cell Tissue Res. 260, 387 (1990).
42. R A. Giannella, M. Luttrell, M. Thompson, Am J. Phys. 245, G492 (1983); M. G. Currie et al., Proc. Natl. Acad. Sci. U.S.A. 89, 947 (1992); M. Field, L. H Graf, W. J Land, P. L. Smith, ibid. 75, 2800 (1978); L. R Forte et al., Am. J. Phys. 263, C607 (1992); M. G. Currie et al., Proc. Natl. Acad. Sci U.S.A 89, 947 (1992).
43. R A. Giannella, M. Luttrell, M. Thompson, Am J. Phys. 245, G492 (1983); M. G. Currie et al., Proc. Natl. Acad. Sci. U.S.A. 89, 947 (1992); M. Field, L. H Graf, W. J Land, P. L. Smith, ibid. 75, 2800 (1978); L. R Forte et al., Am. J. Phys. 263, C607 (1992); M. G. Currie et al., Proc. Natl. Acad. Sci U.S.A 89, 947 (1992).
44. R A. Giannella, M. Luttrell, M. Thompson, Am J. Phys. 245, G492 (1983); M. G. Currie et al., Proc. Natl. Acad. Sci. U.S.A. 89, 947 (1992); M. Field, L. H Graf, W. J Land, P. L. Smith, ibid. 75, 2800 (1978); L. R Forte et al., Am. J. Phys. 263, C607 (1992); M. G. Currie et al., Proc. Natl. Acad. Sci U.S.A 89, 947 (1992).
45. R A. Giannella, M. Luttrell, M. Thompson, Am J. Phys. 245, G492 (1983); M. G. Currie et al., Proc. Natl. Acad. Sci. U.S.A. 89, 947 (1992); M. Field, L. H Graf, W. J Land, P. L. Smith, ibid. 75, 2800 (1978); L. R Forte et al., Am. J. Phys. 263, C607 (1992); M. G. Currie et al., Proc. Natl. Acad. Sci U.S.A 89, 947 (1992).
46. R A. Giannella, M. Luttrell, M. Thompson, Am J. Phys. 245, G492 (1983); M. G. Currie et al., Proc. Natl. Acad. Sci. U.S.A. 89, 947 (1992); M. Field, L. H Graf, W. J Land, P. L. Smith, ibid. 75, 2800 (1978); L. R Forte et al., Am. J. Phys. 263, C607 (1992); M. G. Currie et al., Proc. Natl. Acad. Sci U.S.A 89, 947 (1992).
47. Single-letter abbreviations for the amino acid residues are as follows: A, Ala; C, Cys; D, Asp; E, Glu; F, Phe; G, Gly; H, His; I, Ile, K, Lys; L, Leu; M, Met; N, Asn; P, Pro, Q, Gln; R, Arg, S, Ser; T, Thr; V, Val; W, Trp; and Y, Tyr.
48. J Levin and F. B Bang, Throm. Diath. Haemorrh 19, 186 (1968); T J. Novitsky, Oceanus 27, 13 (1984).
49. J Levin and F. B Bang, Throm. Diath. Haemorrh 19, 186 (1968); T J. Novitsky, Oceanus 27, 13 (1984).
50. C Q.-Y. Zeng, M. J. Wentz, J. Cohen, M. K. Estes, R F. Ramig, J. Virol., in press.
51. Supported in part by Public Health Service award DK 30144 from NIH. The authors acknowledge K Islam for his assistance in the purification of the synthetic peptides; R. Atmar for statistical analyses; R. Montelaro for helpful discussion, and M. Conner, Y. Dong, D. Graham, S. Henning, R. Javier, and R F Ramig for critical reading of the manuscript