Hepatitis B virus compositions and methods of use
View Patent ↗A polypeptide comprising a preS1 region of hepatitis B virus (HBV), or a fragment thereof, and/or the preS2 region of HBV or a fragment thereof, and methods of use to inhibit virus infection are disclosed. A lentivirus comprising hepatitis B virus (HBV) envelope proteins, or a fragment thereof, and/or the L envelope protein of HBV and/or the M envelope protein of HBV or a fragment thereof, and/or the S envelope protein of HBV or a fragment thereof, and methods of use of this lentivirus HBV pseudovirus as a gene therapy to target hepatocytes for the administration of therapeutic agents are also disclosed.
1. A secreted recombinant polypeptide comprising a preS1 region, wherein the preS1 region consists of the first 30 contiguous amino acids of the sequence of preS1 region of the adw2 serotype of HBV (SEQ ID NO: 2), wherein the polypeptide is capable of inhibiting HBV and/or HDV infection of hepatocytes, further wherein the polypeptide does not contain amino acids of the sequence of the S region of HBV.
2. The polypeptide of claim 1 , wherein the virus infection is by HBV.
3. The polypeptide of claim 1 , wherein the virus infection is by HBV and HDV.
4. The polypeptide of claim 1 , wherein the 30 contiguous amino acids include the first 30 amino acids of preS1 region of HBV.
5. The polypeptide of claim 1 , wherein the sequence of preS1 is fused to a constant domain sequence of an immunoglobulin.
6. The polypeptide of claim 5 , wherein the immunoglobulin is selected from the group consisting of IgG-1, IgG-2, IgG-3, IgG-4, IgA, IgE, IgD, and IgM.
7. The polypeptide of claim 1 , wherein the sequence of preS1 is fused to a sequence of preS2 region of HBV, thereby forming a polypeptide designated as S1S2.
8. The polypeptide of claim 7 , wherein the S1S2 polypeptide is further fused to an immunoglobulin sequence.
9. The polypeptide of claim 1 , wherein the polypeptide is myristoylated.
10. A method of in vivo inhibition of hepatocyte infection, the method comprising administering to an animal in need thereof an effective amount of an isolated nucleic acid sequence encoding a secreted fusion polypeptide comprising: 1) a preS1 region, wherein the preS1 region consists of the first 30 contiguous amino acids of the sequence of preS1 region of the adw2 serotype of HBV (SEQ ID NO: 2); and 2) a constant domain sequence of an immunoglobulin or a sequence of preS2 region of HBV, wherein the polypeptide is capable of inhibiting HBV and/or HDV virus infection of hepatocytes.
11. The method of claim 10 , wherein the hepatocyte infection is by HBV.
12. The method of claim 10 , wherein the hepatocyte infection is by HBV and HDV.
13. The method of claim 10 , wherein the sequence of preS1 is fused to a constant domain sequence of an immunoglobulin.
14. The method of claim 13 , wherein the immunoglobulin is selected from the group consisting of IgG-1, IgG-2, IgG-3, IgG-4, IgA, IgE, IgD, and IgM.
15. The method of claim 10 , wherein the sequence of preS1 is fused to a sequence of preS2 region of HBV, thereby forming a polypeptide designated as S1S2.
16. The method of claim 15 , wherein the S1S2 polypeptide is further fused to an immunoglobulin sequence.
17. The method of claim 10 , wherein the polypeptide is myristoylated.
18. An isolated polynucleotide encoding a polypeptide comprising a preS1 region, wherein the preS1 region consists of the first 30 contiguous amino acids of the sequence of preS1 region of the adw2 serotype of HBV (SEQ ID NO: 2), wherein the polypeptide is capable of inhibiting HBV and/or HDV virus infection of hepatocytes, further wherein the polypeptide does not contain amino acids of the sequence of the S region of HBV.
19. A method of in vivo inhibition of hepatocyte infection, the method comprising administering to an animal in need thereof an effective amount of an isolated secreted fusion polypeptide comprising: 1) a preS1 region, wherein the preS1 region consists of the first 30 contiguous amino acids of the sequence of preS1 region of the adw2 serotype of HBV (SEQ ID NO: 2); and 2) a constant domain sequence of an immunoglobulin or a sequence of preS2 region of HBV, wherein the polypeptide is capable of inhibiting HBV and/or HDV virus infection of hepatocytes.