Herpes simplex virus mutant ICP0 protein
View Patent ↗A mutant virus of herpes simplex virus type 1 (HSV-1) can include a mutant protein involved in replication so as to impair or inhibit replication of HSV-1. The mutant HSV-1 can have a mutation in at least one phosphorylation site of a protein involved in replication in order to inhibit phosphorylation of the site so as to prohibit or impair replication of HSV-1 and/or the clinical severity of HSV-1-mediated diseases. The mutant protein can be a mutant ICP0 that has reduced or inhibited posttranslational phosphorylation. The mutant HSV-1 and/or mutant ICP0 can be used in vaccines or other pharmaceutical preparations to treat, limit and/or prevent HSV-1 infection. The mutant HSV-1 and/or mutant ICP0 can also be used in screening and/or developing anti-HSV-1 agents.
1. A mutant herpes simplex virus type 1 (HSV-1) comprising:
a mutant infected cell protein 0 (ICP0) of HSV-1 having a mutation in at least one phosphorylation site between amino acid 505 and amino acid 528, said mutation being configured to inhibit phosphorylation of said at least one phosphorylation site.
2. A mutant HSV as in claim 1 , wherein the mutation is an amino acid substitution, insertion, deletion, or combination thereof.
3. A mutant HSV as in claim 2 , wherein the mutation is a substitution of at least one serine and/or threonine amino acid between amino acid 505 and amino acid 528 with a different amino acid.
4. A mutant HSV as in claim 2 , wherein the mutation is a substitution of at least one serine and/or threonine amino acid between amino acid 505 and amino acid 528 with an alanine amino acid.
5. A mutant HSV as in claim 3 , wherein the mutation is a substitution of at least one serine and/or threonine amino acid in at least one of amino acids S508, S514, S517, or T518 with a phosphorylation-inhibiting amino acid.
6. A mutant HSV as in claim 5 , wherein the mutations correspond with SEQ ID NO: 2 or 4.
7. A mutant HSV as in claim 1 , wherein the mutant HSV-1 is disposed in an immunogenic composition.
8. A mutant simplex virus type 2 (HSV-2) comprising:
a mutant infected cell protein 0 (ICP0) of HSV-2 having a mutation in at least one phosphorylation site between amino acid 518 and amino acid 531, said mutation being configured to inhibit phosphorylation of said at least one phosphorylation site.
9. A mutant HSV as in claim 8 , wherein the mutation is a substitution of at least one serine and/or threonine amino acid between amino acid 518 and amino acid 531 with a different amino acid.
10. A mutant HSV as in claim 8 , wherein the mutation is a substitution of at least one serine and/or threonine amino acid between amino acid 518 and amino acid 531 with an alanine amino acid.
11. A mutant HSV as in claim 10 , wherein the mutations correspond with SEQ ID NO: 8.
12. A mutant HSV as in claim 8 , wherein the mutant HSV-2 is disposed in an immunogenic composition.
13. An immunogenic composition for herpes simplex virus (HSV), the immunogenic composition comprising:
a pharmaceutically acceptable carrier; and
a mutant infected cell protein 0 (ICP0) of mutant HSV-1 and/or HSV-2 having a mutation in at least one phosphorylation site of the ICP0 protein, the at least one phosphorylation site being between amino acid 505 and amino acid 528 for the HSV-1 ICP0, said mutation being configured to inhibit phosphorylation of said at least one phosphorylation site.
14. An immunogenic composition as in claim 13 , wherein the mutation is an amino acid substitution, insertion, deletion, or combination thereof.
15. An immunogenic composition as in claim 13 , wherein the mutation is a substitution of at least one serine and/or threonine amino acid between amino acid 505 and amino acid 528 with a different amino acid for the HSV-1 ICP0.
16. An immunogenic composition as in claim 13 , wherein the mutation is a substitution of at least one serine and/or threonine amino acid between amino acid 505 and amino acid 528 with an alanine amino acid for the HSV-1 ICP0.
17. An immunogenic composition as in claim 13 , wherein the mutation is a substitution of at least one serine and/or threonine amino acid in at least one of amino acids S508, S514, S517, or T518 with a phosphorylation-inhibiting amino acid for the HSV-1 ICP0.
18. An immunogenic composition as in claim 17 , wherein the mutations correspond with SEQ ID NO: 2 or 4.
19. An immunogenic composition as in claim 14 , wherein the mutation is between amino acid 518 and amino acid 531 for the HSV-2 ICP0.
20. An immunogenic composition as in claim 19 , wherein the mutation is a substitution of at least one serine and/or threonine amino acid between amino acid 518 and amino acid 531 with a different amino acid for the HSV-2 ICP0.
21. An immunogenic composition as in claim 19 , wherein the mutation is a substitution of at least one serine and/or threonine amino acid between amino acid 518 and amino acid 531 with an alanine amino acid for the HSV-2 ICP0.
22. An immunogenic composition as in claim 21 , wherein the mutations correspond with SEQ ID NO: 8.
23. An immunogenic composition as in claim 13 , wherein the mutant ICP0 is disposed in a viral particle within the composition.
24. An immunogenic composition as in claim 19 , wherein the mutation is a substitution of at least one serine and/or threonine amino acid in at least one of amino acids S518 or S530 with a phosphorylation-inhibiting amino acid for the HSV-2 ICP0.
25. A mutant virus as in claim 8 , wherein the mutation is a substitution of at least one serine and/or threonine amino acid in at least one of amino acids S518 or S530 with a phosphorylation-inhibiting amino acid for the HSV-2 ICP0.