Methods for the reactivation of latent HIV using cytosine methylation inhibitors and NF-KB activators
The present disclosure provides methods and compositions for reactivating latent immunodeficiency virus in an immunodeficiency virus-infected cell. The methods generally involve contacting an immunodeficiency virus-infected cell with a synergistically effective amount of an inhibitor of cytosine methylation and an NF-κB activator. The present disclosure provides methods and compositions for reducing the reservoir of latent immunodeficiency virus in an individual, and for treating an immunodeficiency virus infection in an individual.
1. A method of reactivating latent immunodeficiency virus in an immunodeficiency virus-infected cell, the method comprising contacting the cell with a synergistically effective amount of an inhibitor of cytosine methylation and an NF-κB activator, wherein the cytosine methylation inhibitor is 5-aza-2′deoxycytidine, and wherein the NF-κB activator is TNF-α or prostratin, wherein the inhibitor of cytosine methylation and the NF-κB activator synergistically reactivate the latent immunodeficiency virus.
2. A method of reducing the number of cells containing a latent human immunodeficiency virus in an individual, the method comprising:
administering to the individual a synergistically effective amount of an inhibitor of cytosine methylation and an NF-κB activator, wherein the cytosine methylation inhibitor is 5-aza-2′ deoxycytidine, and wherein the NF-κB activator is TNF-α or prostratin.
3. The method of claim 2 , wherein said administering is effective to reduce the number of cells containing a latent human immunodeficiency virus in the individual by at least 20%.
4. The method of claim 1 , wherein the cytosine methylation inhibitor is 5-aza-2′deoxycytidine and wherein the NF-κB activator is TNF-α.
5. The method of claim 1 , wherein the cytosine methylation inhibitor is 5-aza-2′deoxycytidine and wherein the NF-κB activator is prostratin.
6. The method of claim 2 , wherein the cytosine methylation inhibitor is 5-aza-2′deoxycytidine and wherein the NF-κB activator is TNF-α.
7. The method of claim 2 , wherein the cytosine methylation inhibitor is 5-aza-2′deoxycytidine and wherein the NF-κB activator is prostratin.