RING-Domain E3 Ligase-Mediated Host–Virus Interactions: Orchestrating Immune Responses by the Host and Antagonizing Immune Defense by Viruses

Abstract

The RING-domain E3 ligases (RING E3s), a group of E3 ligases containing one or two RING finger domains, are involved in various cellular processes such as cell proliferation, immune regulation, apoptosis, among others. In the host, a substantial number of the RING E3s have been implicated to inhibit viral replication through regulating immune responses, including activation and inhibition of retinoic acid-inducible gene I-like receptors, toll-like receptors, and DNA receptor signaling pathways, modulation of cell-surface expression of major histocompatibility complex, and co-stimulatory molecules. During the course of evolution and adaptation, viruses encode RING E3s to antagonize host immune defense, such as the infected cell protein 0 of herpes simplex virus type 1, the non-structural protein 1 of rotavirus, and the K3 and K5 of Kaposi’s sarcoma-associated herpesvirus. In addition, recent studies suggest that viruses can hijack the host RING E3s to facilitate viral replication. Based on emerging and interesting discoveries, the RING E3s present novel links among the host and viruses. Herein, we focus on the latest research progresses in the RING E3s-mediated host–virus interactions and discuss the outlooks of the RING E3s for future research.

To TRIM or not to TRIM: the balance of host–virus interactions mediated by the ubiquitin system

“…2) [23]. Further interpretations on the importance of the RING family as a whole in coordinating antiviral immune defences can be found in additional reviews [2,5,24,25]. Of particular noteworthiness from within the RING family is a grouping of over 70 members encoded in the human genome known as TRIM proteins [5,23,[26][27][28].…”

RING finger protein 38 induces gastric cancer cell growth by decreasing the stability of the protein tyrosine phosphatase SHP‐1

“…The UPS is ATP-dependent and three classes of enzymes are required for mediating protein ubiquitination, including ubiquitin-activating enzyme E1, ubiquitinconjugating enzyme E2 and ubiquitin ligase E3 [20][21][22]. Among these, E3 ubiquitin ligases represent highly attractive protein targets for drug discovery, because the significance of E3 ligases as prospective targets for small molecule modulation is reinforced by ever growing evidences of their roles in tumors and other diseases [23,24].…”

Polinton-like viruses and virophages are widespread in aquatic ecosystems

“…Similarly, 61 viruses in our dataset, across all virus groups (apart from the S. Punctatus and CHI groups) contained a predicted E3 ubiquitin-protein ligase. E3 ligases are known to counter host immune defenses in vertebrate viruses 27 , they have previously been detected in one other PLV 11 . Interestingly, there was a further group of 12 virophages from VC_34 which encoded a Cas4-like nuclease (Figure 2).…”