Apolipoprotein E polypeptides and their use
Disclosed herein are several apoplipoprotein E (ApoE) polypeptides, and nucleic acids encoding these polypeptides, that can be used to treat or prevent a hepatitis infection in a subject, such as a hepatitis C virus infection. These ApoE polypeptides can inhibit the entry of hepatitis C virus into cells, and inhibit viral replication. Nucleic acids encoding these polypeptides are also disclosed, as well as methods for their preparation.
1. A method of treating and/or inhibiting a hepatitis virus infection in a subject, comprising:
selecting a subject with a hepatitis C virus infection, and
administering to the subject a therapeutically effective amount of an isolated polypeptide, wherein a) the polypeptide comprises the amino acid sequence set forth as SEQ ID NO: 1, the polypeptide is between 29 and 66 amino acids in length, the polypeptide comprises an N-terminal cysteine, and the polypeptide can inhibit the entry of a hepatitis C virus into a cell, and/or b) administering to the subject a therapeutically effective amount of a dimer of two polypeptides wherein each of the of e tides has a c steine at its N-terminus, is 29 to 66 amino acids in length, and comprises the amino acid sequence set forth as SEQ ID NO: 1, wherein the polypeptides are linked by a covalent bond between the cysteines to form the dimer, and wherein the dimer can inhibit the entry of a hepatitis C virus into a cell,
thereby treating and/or inhibiting the hepatitis C virus infection in the subject.
2. The method of claim 1 , wherein the subject does not have high cholesterol.
3. The method of claim 1 , wherein the subject has an acute infection with hepatitis C.
4. The method of claim 1 , wherein the subject has a chronic infection with hepatitis C.
5. The method of claim 1 , wherein the subject is a drug abuser who uses needles, a subject exposed to blood products, a subject who has had unprotected sex with an infected subject, or a subject undergoing tattoos or body piercings.
6. The method of claim 1 , further comprising administering a second anti-viral agent to the subject.
7. A method of inhibiting hepatitis C viral replication in a subject infected with a hepatitis C virus, comprising:
administering to the subject a) a therapeutically effective amount of an isolated polypeptide, wherein the polypeptide comprises the amino acid sequence set forth as SEQ ID NO: 1, wherein the polypeptide is between 29 and 66 amino acids in length, the polypeptide comprises an N-terminal cysteine, and the polypeptide can inhibit the entry of a hepatitis C virus into a cell, and/or b) administering to the subject a therapeutically effective amount of a dimer of two polypeptides, wherein each of the polypeptides has a cysteine at its N-terminus, is 29 to 66 amino acids in length, and comprises the amino acid sequence set forth as SEQ ID NO: 1, wherein the polypeptides are linked by a covalent bond between the cysteines to form the dimer, and wherein the dimer can inhibit the entry of a hepatitis C virus into a cell
thereby inhibiting hepatitis C viral replication in the subject.
8. The method of claim 7 , wherein the subject is human.
9. The method of claim 1 , wherein the polypeptide comprises the amino acid sequence set forth as SEQ ID NO: 9.
10. The method of claim 1 , wherein the polypeptide consists of the amino acid sequence set forth as SEQ ID NO: 9.
11. The method of claim 9 , wherein the polypeptide is 32 to 58 amino acids in length.
12. The method of claim 1 , wherein the polypeptide comprises the amino acid sequence set forth as SEQ ID NO: 2 or SEQ ID NO: 8.
13. The method of claim 7 , wherein the polypeptide comprises the amino acid sequence set forth as SEQ ID NO: 9.
14. The method of claim 7 , wherein the polypeptide consists of the amino acid sequence set forth as SEQ ID NO: 9.
15. The method of claim 13 , wherein the polypeptide is 32 to 58 amino acids in length.
16. The method of claim 7 , wherein the polypeptide comprises the amino acid sequence set forth as SEQ ID NO: 2 or SEQ ID NO: 8.
17. The method of claim 7 , wherein the subject does not have high cholesterol.
18. The method of claim 7 , wherein the subject has an acute infection with hepatitis C.
19. The method of claim 7 , wherein the subject has a chronic infection with hepatitis C.
20. The method of claim 7 , wherein the subject is a drug abuser who uses needles, a subject exposed to blood products, a subject who has had unprotected sex with an infected subject, or a subject undergoing tattoos or body piercings.