Abstract: The present disclosure provides for recombinant nucleic acids, and cells and virions comprising the recombinant nucleic acids, that can be used to identify, isolate, and/or purify cells latently infected with immunodeficiency virus. A subject recombinant nucleic acid includes (a) a first nucleotide sequence encoding a first reporter polypeptide that produces a first detectable signal, where the first nucleotide sequence is operably linked to an immunodeficiency virus promoter and is translated as an early gene; and (b) a second nucleotide sequence encoding a second reporter polypeptide that produces a second detectable signal that is distinguishable from the first detectable signal, where the second nucleotide sequence is operably linked to a non-immunodeficiency virus promoter. In some aspects, the first and second nucleotide sequences are both positioned between a shared 5? long terminal repeat (LTR) and a shared 3? LTR. Also provided are related methods.

Abstract: The present disclosure provides methods of reducing the level of acetylated Tau in a neuron or a glial cell in an individual, the methods involving administering to the individual a prodrug that is converted in the individual to salicylate. The present disclosure provides methods of treating a tauopathy in an individual, the methods involving administering to the individual a prodrug that is converted in the individual to salicylate.

Abstract: The present disclosure provides methods of reducing the level of acetylated Tau in a neuron or a glial cell in an individual, the methods involving administering to the individual a prodrug that is converted in the individual to salicylate. The present disclosure provides methods of treating a tauopathy in an individual, the methods involving administering to the individual a prodrug that is converted in the individual to salicylate.

Abstract: 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-?B 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.

Abstract: The present disclosure provides for recombinant nucleic acids, and cells and virions comprising the recombinant nucleic acids, that can be used to identify, isolate, and/or purify cells latently infected with immunodeficiency virus. A subject recombinant nucleic acid includes (a) a first nucleotide sequence encoding a first reporter polypeptide that produces a first detectable signal, where the first nucleotide sequence is operably linked to an immunodeficiency virus promoter and is translated as an early gene; and (b) a second nucleotide sequence encoding a second reporter polypeptide that produces a second detectable signal that is distinguishable from the first detectable signal, where the second nucleotide sequence is operably linked to a non-immunodeficiency virus promoter. In some aspects, the first and second nucleotide sequences are both positioned between a shared 5? long terminal repeat (LTR) and a shared 3? LTR. Also provided are related methods.

Abstract: The present disclosure provides compositions and methods for reactivating latent immunodeficiency vims. The methods generally involve contacting an HIV-infected cell in which HIV is latent with an agent that binds a bromodomain (BRD) in the cell. Latently infected cells contain replication-competent integrated HIV-1 genomes that are blocked at the transcriptional level, resulting in the absence of viral protein expression. The present disclosure provides methods for reducing the reservoir of latent immunodeficiency virus in an individual.

Abstract: The present disclosure provides methods of reducing immunodeficiency virus transcription, involving use of diflunisal or an active ester thereof. The disclosure also provides methods of treating an immunodeficiency virus infection in an individual, the method generally involving administering to the individual an effective amount of diflunisal or an active ester thereof.

Abstract: The present disclosure provides a method of increasing an immune response in an individual, the method involving administering to an individual in need thereof an inhibitor of SIRT1. The present disclosure provides a method of reducing an immune response, e.g., to treat chronic immune hyperactivity, the method generally involving administering to an individual in need thereof an activator of SIRT1. The present disclosure provides a method of modulating activation and differentiation of CD4+ T cells.

Abstract: The present invention provides methods of detecting cells showing smooth muscle differentiation. The present invention further provides methods of detecting tumor cells. The present invention further provides compositions and methods for treating smooth muscle cell disorders.

Abstract: 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.

Abstract: The present invention provides methods for identifying agents that modulate a level or an activity of tubulin deacetylase polypeptide, as well as agents identified by the methods. The invention further provides methods of modulating tubulin deacetylase activity in a cell. The invention further provides methods of modulating cellular proliferation by modulating the activity of tubulin deacetylase.

Abstract: The present disclosure provides a method of increasing an immune response in an individual, the method involving administering to an individual in need thereof an inhibitor of SIRT1. The present disclosure provides a method of reducing an immune response, e.g., to treat chronic immune hyperactivity, the method generally involving administering to an individual in need thereof an activator of SIRT1. The present disclosure provides a method of modulating activation and differentiation of CD4+T cells.

Abstract: The present invention provides nucleic acid molecules that encode histone deacetylase, as well as recombinant vectors and host cells that include the subject nucleic acid molecules. Also provided are histone deacetylase polypeptide compositions. The histone deacteylase nucleic acid molecules are useful in a variety of diagnostic and therapeutic applications, which are also provided.

Abstract: The present invention provides treatment methods involving modulating a sirtuin activity and/or a sirtuin mRNA and/or a sirtuin polypeptide level. In some embodiments, the present invention provides treatment methods involving modulating SIRT1 activity and/or SIRT mRNA and/or polypeptide level. The present invention provides methods of inhibiting SIRT1 Tat deacetylase activity. Methods of inhibiting SIRT1 Tat deacetylase activity are useful for treating immunodeficiency virus infections, particularly human immunodeficiency virus (HIV) infection. Thus, the present invention provides methods of treating an immunodeficiency virus infection, generally involving inhibiting SIRT1 Tat deacetylase activity. The present invention further provides methods of identifying agents that modulate sirtuin activity (e.g., SIRT1 activity), particularly ability of sirtuins to interact with (e.g., bind and/or deacetylate) a substrate, e.g., a viral substrate such as a Tat polypeptide.

Abstract: The present invention provides methods of detecting cells showing smooth muscle differentiation. The present invention further provides methods of detecting tumor cells. The present invention further provides compositions and methods for treating smooth muscle cell disorders.

Abstract: The present invention provides isolated cells that comprise, integrated into the genome of the cell, a transcription-competent immunodeficiency virus or a transcription-competent immunodeficiency virus-based retroviral vector. Under basal in vitro culture conditions, the immunodeficiency virus is latent, and the expression of the latent immunodeficiency virus can be reactivated. The invention farther provides methods of making a subject cell. The invention further provides screening methods for identifying agents that activate a latent immunodeficiency virus; and screening method for identifying agents that block reactivation of latent immunodeficiency virus expression in response to T cell activation signals. The invention further provides agents identified in the subject screening assays. The invention further provides methods of treating an immunodeficiency virus infection.

Abstract: The present invention provides treatment methods involving modulating a sirtuin activity and/or a sirtuin mRNA and/or a sirtuin polypeptide level. In some embodiments, the present invention provides treatment methods involving modulating SIRT1 activity and/or SIRT mRNA and/or polypeptide level. The present invention provides methods of inhibiting SIRT1 Tat deacetylase activity. Methods of inhibiting SIRT1 Tat deacetylase activity are useful for treating immunodeficiency virus infections, particularly human immunodeficiency virus (HIV) infection. Thus, the present invention provides methods of treating an immunodeficiency virus infection, generally involving inhibiting SIRT1 Tat deacetylase activity. The present invention further provides methods of identifying agents that modulate sirtuin activity (e.g., SIRT1 activity), particularly ability of sirtuins to interact with (e.g., bind and/or deacetylate) a substrate, e.g., a viral substrate such as a Tat polypeptide.

Abstract: The present invention provides methods for identifying agents that modulate a level or an activity of tubulin deacetylase polypeptide, as well as agents identified by the methods. The invention further provides methods of modulating tubulin deacetylase activity in a cell. The invention further provides methods of modulating cellular proliferation by modulating the activity of tubulin deacetylase.

Abstract: The present invention provides methods for identifying agents that modulate a level or an activity of a mitochondrial NAD-dependent deacetylase polypeptide, as well as agents identified by the methods. The invention further provides methods of modulating mitochondrial NAD-dependent deacetylase activity in a cell. The invention further provides methods of modulating mitochondrial function by modulating the activity of mitochondrial NAD-dependent deacetylase.

Abstract: The present invention provides methods for identifying agents that modulate a level or an activity of tubulin deacetylase polypeptide, as well as agents identified by the methods. The invention further provides methods of modulating tubulin deacetylase activity in a cell. The invention further provides methods of modulating cellular proliferation by modulating the activity of tubulin deacetylase.