RING finger protein 5 is a key anti-FMDV host factor through inhibition of virion assembly

PLoS Pathogens, Journal Year: 2025, Volume and Issue: 21(1), P. e1012848 - e1012848

Published: Jan. 17, 2025

Foot-and-mouth disease virus (FMDV) are small, icosahedral viruses that cause serious clinical symptoms in livestock. The FMDV VP1 protein is a key structural component, facilitating entry. Here, we find the E3 ligase RNF5 interacts with and targets it for degradation through ubiquitination at lys200 of VP1, ultimately inhibiting replication. Mutations this lysine site have been found to increase replication mice. Importantly, pharmacological activator Analog-1 alleviates development mouse infection model. Furthermore, recognizes from several picornaviruses, suggesting targeting may be broad-spectrum antiviral strategy. These findings shed light on role ubiquitin-proteasome system controlling replication, offering potential new strategies treating viral infections.

Language: Английский

RNF5 inhibits HBV replication by mediating caspase-3-dependent degradation of core protein

Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 16

Published: April 1, 2025

The RING finger protein 5 (RNF5), an E3 ubiquitin ligase, has demonstrated significant antiviral activity against various viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Kaposi’s sarcoma-associated herpesvirus (KSHV). However, its role in hepatitis B virus (HBV) replication not been previously studied. In this study, we demonstrate that RNF5 effectively inhibits HBV by promoting the degradation of Core through a Caspase-3-dependent pathway. We first show expression is upregulated HBV-infected cells patient samples, suggesting host’s response. Subsequently, investigate mechanism which mediates effect, finding targets for independently ligase activity. mediated rather than proteasomal Interestingly, RNF5’s function does rely on ubiquitination, indicating alternative pathway involving apoptosis-related processes. These findings highlight multifunctional suggest targeting could serve as novel therapeutic approach to control replication, providing new insights into development therapies HBV.

Language: Английский

Ring finger protein 5 mediates STING degradation through ubiquitinating K135 and K155 in a teleost fish

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 11, 2024

Stimulator of interferon genes (STING) is a key connector protein in (IFN) signaling, crucial for IFN induction during the activation antiviral innate immunity. In mammals, ring finger 5 (RNF5) functions as an E3 ubiquitin ligase, mediating STING regulation through K150 ubiquitylation to prevent excessive production. However, mechanisms underlying RNF5's teleost fish remain unknown. This study investigated regulatory role mandarin (

Language: Английский