Abstract: Provided are methods and compositions for generating a deletion library, and methods and compositions for generating and identifying a defective interfering particle (DIP). Also provided are transposon cassettes. A subject method can include: inserting a transposon cassette comprising a target sequence for a sequence specific DNA endonuclease into a population of circular target DNAs to generate a population of transposon-inserted circular target DNAs; contacting the population of transposon-inserted circular target DNAs with the sequence specific DNA endonuclease to generate a population of cleaved linear target DNAs; contacting the population of cleaved linear target DNAs with one or more exonucleases to generate a population of deletion DNAs; and circularizing the deletion DNAs to generate a library of circularized deletion DNAs. The population of circular target DNAs can include viral genomic DNA. Also provided ae human immunodeficiency virus (HIV) deletion mutants, e.g.

Abstract: Described herein are compositions defective SARS-CoV-2 constructs and particles that can interfere with or block infection of uninfected cells and methods for generating such defective SARS-CoV-2 constructs and particles. The compositions and methods described herein are useful for treatment of SARS-CoV-2 infections.

Abstract: Provided are methods and compositions for generating a deletion library, and methods and compositions for generating and identifying a defective interfering particle (DIP). Also provided are transposon cassettes. A subject method can include: inserting a transposon cassette comprising a target sequence for a sequence specific DNA endonuclease into a population of circular target DNAs to generate a population of transposon-inserted circular target DNAs; contacting the population of transposon-inserted circular target DNAs with the sequence specific DNA endonuclease to generate a population of cleaved linear target DNAs; contacting the population of cleaved linear target DNAs with one or more exonucleases to generate a population of deletion DNAs; and circularizing the deletion DNAs to generate a library of circularized deletion DNAs. The population of circular target DNAs can include viral genomic DNA. Also provided are human immunodeficiency virus (HIV) deletion mutants, e.g.

Abstract: The present disclosure provides interfering, conditionally replicating human immunodeficiency virus (HIV) constructs; infectious particles comprising the constructs; and compositions comprising the constructs or the particles. The constructs, particles, and compositions are useful in methods of reducing HIV viral load in an individual, which methods are also provided.

Abstract: The present disclosure provides compositions and methods for inhibiting herpesvirus replication in a cell infected with herpesvirus. The composition includes a double stranded DNA molecule including a sequence of a cis regulatory sequence (crs) of a herpesvirus, wherein the crs is flanked on the 5? end by a first sequence of at least 2 base pairs and on the 3? end by a second sequence of at least 2 base pairs.

Abstract: Provided are methods and compositions for generating a deletion library, and methods and compositions for generating and identifying a defective interfering particle (DIP). Also provided are transposon cassettes. A subject method can include: inserting a transposon cassette comprising a target sequence for a sequence specific DNA endonuclease into a population of circular target DNAs to generate a population of transposon-inserted circular target DNAs; contacting the population of transposon-inserted circular target DNAs with the sequence specific DNA endonuclease to generate a population of cleaved linear target DNAs; contacting the population of cleaved linear target DNAs with one or more exonucleases to generate a population of deletion DNAs; and circularizing the deletion DNAs to generate a library of circularized deletion DNAs. The population of circular target DNAs can include viral genomic DNA. Also provided are human immunodeficiency virus (HIV) deletion mutants, e.g.

Abstract: The present disclosure provides a method for inhibiting cytomegalovirus (CMV) replication in a cell infected with CMV, the method comprising contacting the cell with a bisbenzimidazole compound. The present disclosure provides a method of treating a CMV infection in an individual, the method comprising administering to the individual an effective amount of a bisbenzimidazole compound.

Abstract: A recombinant expression vector comprising a nucleotide sequence encoding a herpesvirus transactivator, where the nucleotide sequence is operably linked to a herpesvirus control element is provided as are cell lines genetically modified to express a herpesvirus transactivator under the control of a herpesvirus control element. Also provided are methods of identifying agents that disrupt feedback regulation of a herpesvirus transcriptional control element by a herpesvirus transactivator.

Abstract: The present disclosure provides a method for inhibiting cytomegalovirus (CMV) replication in a cell infected with CMV, the method comprising contacting the cell with a bisbenzimidazole compound. The present disclosure provides a method of treating a CMV infection in an individual, the method comprising administering to the individual an effective amount of a bisbenzimidazole compound.

Abstract: The present disclosure provides an interfering, conditionally replicating human immunodeficiency virus (HIV) construct; infectious particles comprising the constructs; and compositions comprising the construct or the particle. The constructs, particles, and compositions are useful in methods of reducing HIV viral load in an individual, which methods are also provided.

Abstract: The present disclosure provides an interfering, conditionally replicating human immunodeficiency virus (HIV) construct; infectious particles comprising the constructs; and compositions comprising the construct or the particle. The constructs, particles, and compositions are useful in methods of reducing HIV viral load in an individual, which methods are also provided.

Abstract: The present disclosure provides a recombinant expression vector comprising a nucleotide sequence encoding a herpesvirus transactivator, where the nucleotide sequence is operably linked to a herpesvirus control element. The present disclosure provides cell lines genetically modified to express a herpesvirus transactivator under the control of a herpesvirus control element. The present disclosure provides methods of identifying agents that disrupt feedback regulation of a herpesvirus transcriptional control element by a herpesvirus transactivator.