Cellular genes regulated by HIV-1 infection and methods of use thereof
This invention provides cellular gene products which have anti-apoptotic activity in HIV-1 infected cells and provides agents for the inhibition of the cellular gene products.
1. A method for inducing apoptosis in a target cell comprising contacting the cell with a therapeutically effective amount of at least one inhibitor of HIV-Associated Life Preserver (HALP) activity, thereby inducing apoptosis,
wherein said target cell is infected with a retrovirus, and
wherein said inhibitor is a HALP antisense oligonucleotide or a HALP small interfering double stranded RNA (siRNA) molecule.
2. The method as claimed in claim 1 , wherein said retrovirus is human immunodeficiency virus 1 (HIV-1).
3. The method as claimed in claim 1 , wherein said target cell is transformed with a recombinant expression vector for expressing the antisense oligonucleotide or the siRNA molecule.
4. The method of claim 1 , wherein said inhibitor is administered to said target cell in combination with at least one anti-HIV agent.
5. The method of claim 4 , wherein said anti-HIV agent is selected from the group consisting of protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, and fusion inhibitors.
6. The method of claim 1 , wherein said inhibitor is administered to said target cell in combination with at least one anti-HIV vaccine.
7. The method of claim 1 , wherein said retrovirus is an immunodeficiency virus.
8. The method of claim 1 , wherein said retrovirus is a lentivirus.
9. The method of claim 1 , wherein said retrovirus is selected from the group consisting of human immunodeficiency virus 1 (HIV-1), human immunodeficiency virus 2 (HIV-2), simian immunodeficiency virus (SIV), and feline immunodeficiency virus (FIV).
10. The method of claim 1 , wherein the amino acid sequence of said HALP is SEQ ID NO: 2.
11. The method of claim 1 , wherein said antisense molecule consists of 15 to 30 nucleotides and the sequence of the antisense molecule is complementary to a nucleic acid sequence encoding said HALP, and wherein each strand of said siRNA molecule is between about 12 and 30 nucleotides in length and the sequence of the sense strand of said siRNA molecule is homologous to a nucleic acid sequence encoding said HALP.
12. The method of claim 11 , wherein each strand of said siRNA molecule is between about 12 and 30 nucleotides in length and the sequence of the sense strand of said siRNA molecule is homologous to a nucleic acid sequence encoding said HALP.
13. The method of claim 11 , wherein each strand of said siRNA molecule is about 21 nucleotides.
14. The method of claim 11 , wherein the GC content of said siRNA molecule is about 45% to about 55%.
15. The method of claim 11 , wherein said nucleic acid sequence encoding HALP is SEQ ID NO: 1.
16. A method for treating a patient infected with the human immunodeficiency virus comprising administering to said patient at least one inhibitor of HIV-Associated Life Preserver (HALP) activity in a biologically compatible medium,
wherein said inhibitor is a HALP antisense oligonucleotide or a HALP small interfering double stranded RNA (siRNA) molecule.
17. The method of claim 16 , wherein said inhibitor is administered in combination with at least one anti-HIV agent.
18. The method of claim 17 , wherein said anti-HIV agent is selected from the group consisting of protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, and fusion inhibitors.
19. The method of claim 16 , wherein said antisense oligonucleotide or siRNA molecule are administered to said patient by administering to said patient a recombinant expression vector encoding said antisense oligonucleotide or siRNA molecule.
20. The method of claim 16 , wherein the amino acid sequence of said HALP is SEQ ID NO: 2.
21. The method of claim 16 , wherein said antisense molecule consists of 15 to 30 nucleotides and the sequence of the antisense molecule is complementary to a nucleic acid sequence encoding said HALP, and wherein each strand of said siRNA molecule is between about 12 and 30 nucleotides in length and the sequence of the sense strand of said siRNA molecule is homologous to a nucleic acid sequence encoding said HALP.
22. The method of claim 21 , wherein each strand of said siRNA molecule is between about 12 and 30 nucleotides in length and the sequence of the sense strand of said siRNA molecule is homologous to a nucleic acid sequence encoding said HALP.
23. The method of claim 21 , wherein each strand of said siRNA molecule is about 21 nucleotides.
24. The method of claim 21 , wherein the GC content of said siRNA molecule is about 45% to about 55%.
25. The method of claim 21 , wherein said nucleic acid sequence encoding HALP is SEQ ID NO: 1.