CDK9/cyclin T1: a host cell target for antiretroviral therapy

Abstract

Hijacking of the host cell’s signal transduction machinery has been increasingly regarded as an important strategy for facilitating virus propagation. The positive-transcription elongation factor (P-TEFb) complex, cyclin-dependent kinase (CDK)9/cyclin T1, is an example of such an attack by HIV. Upon infection of cells, the HIV protein transactivator of transcription (Tat) forms a highly specific complex with the two host cell proteins CDK9 and cyclin T1. This complex ensures phosphorylation of the native CDK9 substrate, RNA polymerase II, leading to productive elongation of viral RNA in the host cell. Although challenging, inhibition of CDK9 activity with small molecules is a therapeutically valid strategy to inhibit HIV replication. Other than direct antiviral agents, that inhibit HIV replication through a direct interaction with viral proteins, CDK9 inhibitors might not suffer from the emergence of resistant virus strains. This review outlines the advantages and prospects of selective CDK9 inhibitors in the management of HIV infections.