Compositions and Methods for Modulating Immunodeficiency Virus Transcription
First Claim
1. A method of inhibiting transcription of a human immunodeficiency virus (HIV) in a cell infected with the HIV, the method comprising contacting the cell with an agent that inhibits enzymatic activity of a lysine-specific demethylase-1 (LSD1) polypeptide, that reduces the level of the LSD1 polypeptide in the cell, that reduces LSD1-mediated demethylation of a Tat polypeptide in the cell, or that reduces the level or activity of a CoREST polypeptide, wherein said contacting results in inhibition of HIV transcription.
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Abstract
The present disclosure provides methods of modulating immunodeficiency virus transcription, involving modulating enzymatic activity and/or levels of a lysine-specific demethylase-1 (LSD1) polypeptide and/or LSD1-mediated demethylation of methylated Tat. The present disclosure also provides method of identifying agents that modulate LSD1-mediated demethylation of a human immunodeficiency virus (HIV) Tat polypeptide.
42 Citations
38 Claims
- 1. A method of inhibiting transcription of a human immunodeficiency virus (HIV) in a cell infected with the HIV, the method comprising contacting the cell with an agent that inhibits enzymatic activity of a lysine-specific demethylase-1 (LSD1) polypeptide, that reduces the level of the LSD1 polypeptide in the cell, that reduces LSD1-mediated demethylation of a Tat polypeptide in the cell, or that reduces the level or activity of a CoREST polypeptide, wherein said contacting results in inhibition of HIV transcription.
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3. (canceled)
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9-10. -10. (canceled)
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13. (canceled)
- 14. A method of treating a human immunodeficiency virus (HIV) infection in an individual having an HIV infection, the method comprising administering to the individual an effective amount of an agent that inhibits enzymatic activity of a lysine-specific demethylase-1 (LSD1) polypeptide, that reduces the level of the LSD1 polypeptide in a cell, or that reduces LSD1-mediated demethylation of a Tat polypeptide in a cell.
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16-19. -19. (canceled)
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22-24. -24. (canceled)
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27-29. -29. (canceled)
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30. A method of treating a human immunodeficiency virus (HIV) infection in an individual, the method comprising:
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administering to an individual an effective amount of a first active agent, wherein the first active agent increases lysine-specific demethylase-1 (LSD1) enzymatic activity and/or levels, wherein said first active agent reactivates latent HIV integrated into the genome of a cell in the individual; and administering to the individual an effective amount of a second active agent, wherein the second active agent inhibits an immunodeficiency virus function selected from viral replication, viral protease activity, viral reverse transcriptase activity, viral entry into a cell, viral integrase activity, viral Rev activity, viral Tat activity, viral Nef activity, viral Vpr activity, viral Vpu activity, and viral Vif activity.
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31. (canceled)
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32. An in vitro method for identifying an agent that inhibits transcription of human immunodeficiency virus (HIV), the method comprising:
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a) contacting an LSD1 polypeptide and a methylated HIV Tat polypeptide, with a test agent; and b) determining the effect, if any, of the test agent on the methylation of the Tat polypeptide, wherein a test agent that inhibits demethylation of the methylated Tat polypeptide by the LSD1 polypeptide, compared to the level of methylation of the Tat polypeptide in the absence of the test agent, is considered a candidate agent for inhibition of HIV transcription. - View Dependent Claims (33, 35, 37)
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34. (canceled)
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36. (canceled)
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38-39. -39. (canceled)
Specification