ArticleRedox biology2022
Porcine reproductive and respiratory syndrome virus nsp4 positively regulates cellular cholesterol to inhibit type I interferon production.
Article in Redox biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- Article
- The nicotinamide phosphoribosyltransferase inhibitor FK866 restricts influenza A virus replication by perturbing viral polymerase activity.Journal of virology · 2026Article
- Downmodulation of cholesterol biosynthetic network governs activation of the innate immune response to Japanese encephalitis virus infection.Journal of virology · 2026Article
- STING Degradation by PRRSV Activates HKViruses · 2026Article
- Beyond Viral Restriction: The Metabolic Dimensions of Interferon-Stimulated Genes in Antiviral Immunity.Viruses · 2026Review
- NUDT7 Modulates the UBA52-SREBF1 Signaling Axis to Promote PRRSV Replication via Lipid Synthesis.International journal of biological sciences · 2026Article
- Identification of two conserved B-cell epitopes targeting NSP4 of porcine reproductive and respiratory syndrome virus.BMC veterinary research · 2025Article
- Identification of compounds targeting porcine reproductive and respiratory syndrome virus nsp3 and evaluation of their antiviral efficacy.Virulence · 2025Article
- Multi-omics analysis reveals the mechanism ofmSystems · 2025Article
- Article
- Article
- Strategies and scheming: the war between PRRSV and host cells.Virology journal · 2025Review
- Porcine reproductive and respiratory syndrome virus nsp5 inhibits the activation of the Nrf2/HO-1 pathway by targeting p62 to antagonize its antiviral activity.Journal of virology · 2025Article
- Unveiling the crossroads of STING signaling pathway and metabolic reprogramming: the multifaceted role of the STING in the TME and new prospects in cancer therapies.Cell communication and signaling : CCS · 2025Review
- Enhanced Porcine Reproductive and Respiratory Syndrome Virus Replication in Nsp4- or Nsp2-Overexpressed Marc-145 Cell Lines.Veterinary sciences · 2025Article
- Increased viperin expression induced by avian infectious bronchitis virus inhibits viral replication by restricting cholesterol synthesis: an in vitro study.Veterinary research · 2024Article
- Article
- Unfolding of an RNA G-quadruplex motif in the negative strand genome of porcine reproductive and respiratory syndrome virus by host and viral helicases to promote viral replication.Nucleic acids research · 2023Article
- Metabolomic analysis of pig spleen reveals African swine fever virus infection increased acylcarnitine levels to facilitate viral replication.Journal of virology · 2023Article
- Target Discovery of Matrine against PRRSV in Marc-145 Cells via Activity-Based Protein Profiling.International journal of molecular sciences · 2023Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cellular cholesterol plays an important role in the life cycles of enveloped viruses. Previous studies by our group and other groups have demonstrated that the depletion of cellular cholesterol by methyl-β-cyclodextrin (MβCD) reduces the proliferation of porcine reproductive and respiratory syndrome virus (PRRSV), a porcine Arterivirus that has been devastating the swine industry worldwide for over two decades. However, how PRRSV infection regulates cholesterol synthesis is not fully understood. In this study, we showed that PRRSV infection upregulated the activity of protein phosphatase 2 (PP2A), which subsequently activated 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), the rate-limiting enzyme in the cholesterol synthesis pathway, to increase the levels of cellular cholesterol. By screening the PRRSV-encoded proteins, we showed that nsp4 dominated the upregulation of cellular cholesterol, independently of the 3C-like protease activity of nsp4. A mutation analysis showed that domain I (amino acids 1-80) of PRRSV nsp4 interacted with PR65 alpha (PR65α), the structural subunit, and PP2Ac, the catalytic subunit, of PP2A. Importantly, domain I of nsp4 inhibited Sendai virus-induced interferon β production, and this inhibitory effect was eliminated by Lovastatin, an HMGCR inhibitor, indicating that the upregulation of cellular cholesterol by nsp4 is a strategy used by PRRSV to suppress the antiviral innate immunity of its host. Collectively, we here demonstrated the mechanism by which PRRSV regulates cellular cholesterol synthesis and reported a novel strategy by which PRRSV evades its host's antiviral innate immune response.
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