2. Academic Validation
  3. The systemic lupus erythematosus-associated NCF190H allele synergizes with viral infection to cause mouse lupus but also limits virus spread

The systemic lupus erythematosus-associated NCF190H allele synergizes with viral infection to cause mouse lupus but also limits virus spread

  • Nat Commun. 2025 Feb 13;16(1):1593. doi: 10.1038/s41467-025-56857-z.
Yanpeng Li 1 2,  Ana Coelho 1,  Zhilei Li 3,  Malin Alsved 4,  Qixing Li 2,  Rui Xu 2,  Huqiao Luo 1,  Dongxia Liang 5,  Jing Xu 6,  Kutty Selva Nandakumar 2,  Liesu Meng 5 6,  Jakob Löndahl 4,  Rikard Holmdahl 7 8 9
Affiliations

Affiliations

  • 1 Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
  • 2 SMU-KI United Medical Inflammation Center, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
  • 3 Clinical Pharmacy Division, Department of Pharmacy, Southern University of Science and Technology Hospital, Shenzhen, China.
  • 4 Division of Ergonomics and Aerosol Technology, Faculty of Engineering, Lund University, Lund, Sweden.
  • 5 National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, Second Affiliated Hospital of Xi' an Jiaotong University (Xibei Hospital), Xi' an, China.
  • 6 Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an, China.
  • 7 Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden. rikard.holmdahl@ki.se.
  • 8 SMU-KI United Medical Inflammation Center, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China. rikard.holmdahl@ki.se.
  • 9 National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, Second Affiliated Hospital of Xi' an Jiaotong University (Xibei Hospital), Xi' an, China. rikard.holmdahl@ki.se.
PMID: 39939342 DOI: 10.1038/s41467-025-56857-z
Abstract

Studying how single nucleotide polymorphisms (SNPs) crosstalk with non-autologous factors to cause complex autoimmune diseases is challenging. An amino acid replacement in the neutrophil cytosolic factor 1 (NCF1-339/NCF1R90H) leading to lower Reactive Oxygen Species induction has been reported as the major SNP for systemic lupus erythematosus (SLE). Here we show that Infection with the murine norovirus (MNV) contributes to the induction of lupus in Ncf190H mice. Mutant NCF190H upregulates the IFN-α/JAK1/STAT1 pathway in macrophages and anti-MNV-antibody production. In parallel, the MNV Infection of NCF190H mice upregulates Toll-like Receptor 7 in macrophages, plasmacytoid dendritic cells and B220+ splenocytes, thereby promoting germinal center formation and lupus-associated autoantibodies production. These compounded effects lead to protection against MNV Infection but also glomeruloneph ritis with proteinuria and lupus arthritis in the absence of chemical inducers such as pristane. Our data thus suggest that this SLE-associated SNP, NCF190H, synergizes with MNV Infection to induce the development of mouse lupus.

Figures
Products