GB virus C (hepatitis G virus) E2 glycoprotein as an immunomodulatory agent
GB virus C (GBV-C or hepatitis G virus) is a flavivirus that frequently leads to chronic viremia in humans. The invention provides compositions and methods involving GBV-C E2 polypeptides and peptides for use in modulating immune responses, including inhibition inflammation related to pathogenic T-cell activation.
1. A method of inhibiting immune cell activation comprising administering to a mammalian subject in need thereof a GBV-C E2 peptide or polypeptide, said peptide or polypeptide comprising SEQ ID NO: 8 and no more than 250 consecutive residues of GBV-C E2.
2. The method of claim 1 , wherein said peptide or polypeptide comprises 232 or 250 consecutive residues of GBV-C E2.
3. The method of claim 1 , wherein said peptide or polypeptide is about 232 or 250 residues in length.
4. The method of claim 1 , wherein the peptide or polypeptide comprises a non-GBV-C E2 sequence.
5. The method of claim 4 , wherein the non-GBV-C E2 sequence is a cell permeability peptide.
6. The method of claim 1 , wherein the immune cell is a T cell or a B cell.
7. The method of claim 4 , wherein the T cell is a helper T cell, a suppressor T cell, an NK cell or a killer T cell.
8. The method of claim 1 , wherein said subject is a human.
9. The method of claim 1 , wherein administering comprises intravenous, intra-arterial, oral, subcutaneous, topical or intraperitoneal administration.
10. The method of claim 1 , further comprising administering a second anti-inflammatory agent.
11. The method of claim 1 , wherein said peptide or polypeptide is administered at 0.1-500 mg/kg/d.
12. The method of claim 1 , wherein said peptide or polypeptide is administered daily or weekly.
13. The method of claim 1 , wherein said subject suffers from a T cell- or B-cell-mediated inflammatory disease or an IL-2-mediated inflammatory disease.
14. A method of inhibiting IL-2 release, inhibiting inflammation, and/or inhibiting STATS-mediated signaling in a mammalian subject comprising administering to said subject a peptide or polypeptide, said peptide or polypeptide comprising SEQ ID NO: 8 and no more than 250 consecutive residues of GBV-C E2.
15. A pharmaceutical formulation comprising an isolated peptide comprising (a) SEQ ID NO: 8 and no more than 250 consecutive residues of GBV-C E2 fused to a cell permeability peptide; and (b) a pharmaceutically acceptable diluent, carrier or buffer.
16. The pharmaceutical formulation of claim 15 , wherein said peptide comprises 232 or 250 consecutive residues of GBV-C E2.
17. The pharmaceutical formulation of claim 15 , wherein said peptide is about 232 or 250 residues in length.
18. The method of claim 5 , wherein said cell permeability peptide is HIV TAT.
19. The pharmaceutical formulation of claim 15 , wherein said cell permeability peptide is HIV TAT.