Host Restriction Factors and Human Immunodeficiency Virus (HIV-1): A Dynamic Interplay Involving All Phases of the Viral Life Cycle

摘要

Mammalian cells have evolved several mechanisms to prevent or block lentiviral infectionand spread. Among the innate immune mechanisms, the signaling cascade triggered by type Iinterferon (IFN) plays a pivotal role in limiting the burden of HIV-1. In the presence of IFN, humancells upregulate the expression of a number of genes, referred to as IFN-stimulated genes (ISGs),many of them acting as antiviral restriction factors (RFs). RFs are dominant proteins that target differentessential steps of the viral cycle, thereby providing an early line of defense against the virus.The identification and characterization of RFs have provided unique insights into the molecular biologyof HIV-1, further revealing the complex host-pathogen interplay that characterizes the infection.The presence of RFs drove viral evolution, forcing the virus to develop specific proteins tocounteract their activity. The knowledge of the mechanisms that prevent viral infection and their viralcounterparts may offer new insights to improve current antiviral strategies. This review providesan overview of the RFs targeting HIV-1 replication and the mechanisms that regulate their expressionas well as their impact on viral replication and the clinical course of the disease.