HIV accessory proteins versus host restriction factors

Abstract

Primate immunodeficiency viruses, including HIV-1, are characterized by the presence of accessory genes such as vif, vpr, vpx, vpu, and nef. Current knowledge indicates that none of the primate lentiviral accessory proteins has enzymatic activity. Instead, these proteins interact with cellular ligands to either act as adapter molecules to redirect the normal function of host factors for virus-specific purposes or to inhibit a normal host function by mediating degradation or causing intracellular mislocalization/sequestration of the factors involved. This review aims at providing an update of our current understanding of how Vif, Vpu, and Vpx control the cellular restriction factors APOBEC3G, BST-2, and SAMHD1, respectively.

Figure 1

HIV accessory proteins function as adapter molecules. HIV accessory proteins have no enzymatic activity. Instead, they act as adaptor molecules to connect cellular substrates to other cellular pathways such as E3 ubiquitin ligases that then trigger ubiquitination and degradation of the substrates. In some cases, they connect their substrate to adapter protein (AP) complexes that trigger internalization and subsequent lysosomal degradation of the substrate. In most cases, the viral adapter molecule is recycled. Substrates are shown on the left and effectors on the right. For recent reviews on the function of Nef and Vpr see [–81].