Role of host immune responses in sequence variability of HIV-1 Vpu

Viral protein U(Vpu) is an accessory protein associated with two main functions important in human immunodeficiency virus type 1(HIV-1) replication and dissemination; these are down-regulation of CD4 receptor through mediating its proteasomal degradation and enhancement of virion release by antagonizing tetherin/BST2. It is also well established that Vpu is one of the most highly variable proteins in the HIV-1 proteome. However it is still unclear what drives Vpu sequence variability, whether Vpu acquires polymorphisms as a means of immune escape, functional advantage, or otherwise. It is assumed that the host-pathogen interaction is a cause of polymorphic phenotype of Vpu and that the resulting functional heterogeneity of Vpu may have critical significance in vivo. In order to comprehensively understand Vpu variability, it is important to integrate at the population level the genetic associationapproaches to identify specific amino acid residues and the immune escape kinetics which may impose Vpu functional constraints in vivo. This review will focus on HIV-1 accessory protein Vpu in the context of its sequence variability at population level and also bring forward evidence on the role of the host immune responses in driving Vpu sequence variability; we will also highlight the recent findings that illustrate Vpu functional implication in HIV-1 pathogenesis.