Role of the Ubiquitin Proteasome System (UPS) in the HIV-1 Life Cycle

Abstract

Given that the ubiquitin proteasome system (UPS) is the major protein degradation process in the regulation of a wide variety of cellular processes in eukaryotic cells, including alteration of cellular location, modulation of protein activity, and regulation of protein interaction, it is reasonable to suggest that the infecting HIV-1 and the invaded hosts exploit the UPS in a contest for survival and proliferation. However, to date, regulation of the HIV-1 life cycle has been mainly explained by the stage-specific expression of HIV-1 viral genes, not by elimination processes of the synthesized proteins after completion of their duties in the infected cells, which is also quintessential for understanding the molecular processes of the virus life cycle and thereby HIV-1 pathogenesis. In fact, several previous publications have indicated that the UPS plays a critical role in the regulation of the proteasomal degradation of viral and cellular counterparts at every step of the HIV-1 life cycle, from the virus entry to release of the assembled virus particles, which is integral for the regulation of survival and proliferation of the infecting HIV-1 and to replication restriction of the invading virus in the host. However, it is unknown whether and how these individual events taking place at different stages of the HIV-1 life cycle are orchestrated as an overall strategy to overcome the restrictions conferred by the host cells. Thus, in this review, we overview the interplay between HIV-1 viral and cellular proteins for restrictions/competitions for proliferation of the virus in the infected cell, which could open a new avenue for the development of therapeutics against HIV-1 via targeting a specific step of the proteasome degradation pathway during the HIV-1 life cycle.

Keywords: E3 ligase; HIV-1; HIV-1 viral proteins; proteasomal degradation; ubiquitin; ubiquitin proteasome system.

Figure 1

Schematic representation of the HIV-1 life cycle. Each step of the HIV-1 life cycle is underlined, and the viral and cellular proteins involved in each step of the proteasomal regulation are shown as red and teal, respectively. Proteasomal regulation between viral proteins is depicted as a dotted line. See the text for the detailed description of the role of the indicated viral and cellular proteins for the proteasomal degradation processes.