The Ubiquitin-Conjugating System: Multiple Roles in Viral Replication and Infection

Abstract

Through the combined action of ubiquitinating and deubiquitinating enzymes, conjugation of ubiquitin to a target protein acts as a reversible post-translational modification functionally similar to phosphorylation. Indeed, ubiquitination is more and more recognized as a central process for the fine regulation of many cellular pathways. Due to their nature as obligate intracellular parasites, viruses rely on the most conserved host cell machineries for their own replication. Thus, it is not surprising that members from almost every viral family are challenged by ubiquitin mediated mechanisms in different steps of their life cycle and have evolved in order to by-pass or exploit the cellular ubiquitin conjugating system to maximize their chance to establish a successful infection. In this review we will present several examples of the complex interplay that links viruses and the ubiquitin conjugation machinery, with a special focus on the mechanisms evolved by the human immunodeficiency virus to escape from cellular restriction factors and to exit from infected cells.

Degrons in cancer

“…The relevance of this to cancer is evidenced by viruses being collectively responsible for 16% of worldwide cancer incidence (257). To date, seven human oncoviruses have been identified: EpsteinBarr virus (EBV), hepatitis B virus (HBV), human T-lymphotropic virus 1 (HTLV I), human papillomaviruses (HPV16 and HPV18), hepatitis C virus (HCV), Kaposi sarcoma-associated herpesvirus (KSHV), and Merkel cell polyomavirus (MCV) (258). All seven of them use various strategies of interfering with certain degradation events of the host cell (258,259).…”

“…To date, seven human oncoviruses have been identified: EpsteinBarr virus (EBV), hepatitis B virus (HBV), human T-lymphotropic virus 1 (HTLV I), human papillomaviruses (HPV16 and HPV18), hepatitis C virus (HCV), Kaposi sarcoma-associated herpesvirus (KSHV), and Merkel cell polyomavirus (MCV) (258). All seven of them use various strategies of interfering with certain degradation events of the host cell (258,259). Similar to other viruses, oncoviruses modulate the host UPS (258) during viral entry and early after viral entry into the cell (260), as well as during other steps of viral life cycle (261,262).…”

Ubiquitin in Influenza Virus Entry and Innate Immunity

“…Viruses have evolved a large arsenal of strategies to exploit processes regulated by ubiquitin (for a detailed review, refer to [14,15]). They may target unwanted cellular proteins for degradation by K48-linked polyubiquitination or revert undesirable ubiquitination events through deubiquitination.…”

“…Such a treatment not only blocks the ubiquitin proteasome system (UPS), but also depletes the cellular pool of free ubiquitin, affecting many of the cellular pathways involving ubiquitin. Functional UPS is important for the replication of major human pathogens such as herpesviruses, poxviruses, hepadnaviruses, adenoviruses, influenzaviruses, retroviruses, coronaviruses, paramyxoviruses, picornaviruses and rotaviruses [14]. UPS components are upregulated in primary human airway epithelial cells infected by influenza A virus (IAV) [17].…”

Polyploidy and Mitotic Cell Death Are Two Distinct HIV-1 Vpr-Driven Outcomes in Renal Tubule Epithelial Cells

“…Briefly, E3 ubiquitin ligases catalyze the attachment of ubiquitin protein chains to cellular proteins, thus targeting them for destruction by the proteosome. While cells use this ubiquitin proteasome system (UPS) to regulate processes such as DNA repair, DNA replication and transcription, multiple viruses are known to hijack the UPS to manipulate host responses and cellular environments (reviewed in [128]). Multiple studies determined that proteasome---mediated protein degradation via the VPRBP---DDB1---CUL4 E3---ligase complex is critical to Vpr---mediated ATR activation and G2 arrest [129---134].…”