PRRSV Non-Structural Proteins Orchestrate Porcine E3 Ubiquitin Ligase RNF122 to Promote PRRSV Proliferation

Area of Science:

• Virology
• Immunology
• Molecular Biology

Background:

• Ubiquitination is crucial for immune regulation during viral infections.
• Porcine E3 ubiquitin ligase RNF122 is upregulated during Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) infection.

Purpose of the Study:

• To investigate the role of RNF122 in PRRSV infection and its underlying molecular mechanisms.
• To elucidate how PRRSV manipulates host factors for viral propagation.

Main Methods:

• Promoter analysis to identify the core promoter region of RNF122.
• Investigation of transcription factor interactions (HLTF, E2F) with PRRSV non-structural proteins (nsp1α, nsp7, nsp9).
• Ubiquitination assays to determine RNF122's targets (nsp4, MDA5) and linkage types (K63, K27, K48).

Main Results:

• The core promoter of RNF122 is located between -550 to -470 bp upstream of the transcription start site.
• PRRSV nsp1α, nsp7, and nsp9 proteins modulate RNF122 transcription and expression via HLTF and E2F.
• RNF122 stabilizes PRRSV nsp4 via K63-linked ubiquitination, promoting viral replication.
• RNF122 mediates K27- and K48-linked ubiquitination of MDA5, leading to its degradation and inhibition of interferon production.

Conclusions:

• PRRSV utilizes RNF122 as a key factor to enhance viral nsp4 stability and antagonize host interferon (IFNα/β) production, representing a novel immune escape strategy.
• This study deepens understanding of how PRRSV proteins manipulate host factors to counteract innate immunity.
• Findings offer potential targets for antiviral drug development against PRRSV.