Salvinaz Islam Moutusy

All Publications

• EBV reprograms autoreactive anti-CNS B cells as antigen presenting cells in multiple sclerosis. bioRxiv : the preprint server for biology Younis, S., Rasouli, S., Loeffler, J. W., Sattarnezhad, N., Courtney, Y., Moutusy, S. I., Jahanbani, S., Pandit, M., Tomczak, A., Wong, H. H., Sharpe, O., Utz, P. J., Meffre, E., Kipp, L. B., Dunn, J. E., Lanz, T. V., Steinman, L., Robinson, W. H. 2026

  Abstract

  Multiple sclerosis (MS) is a chronic autoimmune disease targeting the central nervous system (CNS). MS develops almost exclusively in individuals previously infected with Epstein-Barr virus (EBV)1, yet the mechanisms linking EBV infection to MS pathogenesis remain incompletely defined. Here we characterized EBV-infected B cells in MS and demonstrated that EBV directly infects autoreactive anti-CNS antigen B cells and reprograms them into pro-inflammatory antigen-presenting cells (APCs). EBV+ B cells in MS were enriched within the CD27+CD21low memory B-cell subset and exhibited upregulated B cell activation and APC transcriptional programs. Recombinant antibodies derived from MS blood and cerebrospinal fluid (CSF) EBV+ B cells bound brain tissue, and several cross-bound both MS-associated autoantigens and Epstein-Barr virus nuclear antigen-1 (EBNA1). In vitro, EBV+ B cells functioned as APCs that stimulated T peripheral helper cells, with associated activation of EBV- anti-CNS antigen B cells. Collectively, these findings support a mechanistic framework in which EBV infects and transcriptionally reprograms autoreactive anti-CNS antigen B cells into APCs that drive pathogenic anti-CNS antigen T cell and EBV- B cell responses in MS.

  View details for DOI 10.64898/2026.02.11.701910

  View details for PubMedID 41727017

  View details for PubMedCentralID PMC12919047

• Epstein-Barr virus reprograms autoreactive B cells as antigen-presenting cells in systemic lupus erythematosus. Science translational medicine Younis, S., Moutusy, S. I., Rasouli, S., Jahanbani, S., Pandit, M., Wu, X., Acharya, S., Sharpe, O., Wijeratne, T. U., Harris, M. L., Yang, E. Y., Chaichian, Y., Parsafar, S., Baker, M. C., Harley, J. B., Meffre, E., Steinman, L., Marshak-Rothstein, A., James, J. A., Martinez, O. M., Utz, P. J., Orange, D. E., Lanz, T. V., Robinson, W. H. 2025; 17 (824): eady0210

  Abstract

  Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by antinuclear antibodies (ANAs). Epstein-Barr virus (EBV) infection has been epidemiologically associated with SLE, yet its role in pathogenesis remains incompletely defined. Here, we developed an EBV-specific single-cell RNA-sequencing platform and used it to demonstrate that EBV infection reprograms autoreactive antinuclear antigen B cells to drive autoimmunity in SLE. We demonstrated that, in SLE, EBV+ B cells are predominantly CD27+CD21low memory B cells that are present at increased frequencies and express ZEB2, TBX21 (T-bet), and antigen-presenting cell transcriptional pathways. Integrative analysis of chromatin immunoprecipitation sequencing (ChIP-seq), assay for transposase-accessible chromatin sequencing (ATAC-seq), and RNA polymerase II occupancy data revealed EBV nuclear antigen 2 (EBNA2) binding at the transcriptional start sites and regulatory regions of CD27, ZEB2, and TBX21, as well as the antigen-presenting cell genes demonstrated to be up-regulated in SLE EBV+ B cells. We expressed recombinant antibodies from SLE EBV+ B cells and demonstrated that they bind prototypical SLE nuclear autoantigens, whereas those from healthy individuals do not. We further found that SLE EBV+ B cells can serve as antigen-presenting cells to drive activation of T peripheral helper cells with concomitant activation of related EBV- antinuclear double-negative 2 B cells and plasmablasts. Our results provide a mechanistic basis for EBV being a driver of SLE through infecting and reprogramming nuclear antigen-reactive B cells to become activated antigen-presenting cells with the potential to promote systemic disease-driving autoimmune responses.

  View details for DOI 10.1126/scitranslmed.ady0210

  View details for PubMedID 41223250

• Memory B Cell Activation and Dysregulation in Systemic Lupus Erythematosus Younis, S., Moutusy, S., Jahanbani, S., Wu, X., Harris, M., Pandit, M., van Dam, L., Sharpe, O., Utz, P., Robinson, W. WILEY. 2024: 3653-3655

  View details for Web of Science ID 001331419105219

• Gut Microbiome-Related Anti-Inflammatory Effects of Aryl Hydrocarbon Receptor Activation on Inflammatory Bowel Disease INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Moutusy, S., Ohsako, S. 2024; 25 (6)

  Abstract

  Inflammatory bowel disease (IBD) is one of the most prevalent chronic inflammations of the gastrointestinal tract (GIT). The gut microbial population, the cytokine milieu, the aryl hydrocarbon receptor (AHR) expressed by immune and nonimmune cells and the intrinsic pathway of Th-cell differentiation are implicated in the immunopathology of IBD. AHR activation requires a delicate balance between regulatory and effector T-cells; loss of this balance can cause local gut microbial dysbiosis and intestinal inflammation. Thus, the study of the gut microbiome in association with AHR provides critical insights into IBD pathogenesis and interventions. This review will focus on the recent advancements to form conceptional frameworks on the benefits of AHR activation by commensal gut bacteria in IBD.

  View details for DOI 10.3390/ijms25063372

  View details for Web of Science ID 001192885500001

  View details for PubMedID 38542367

  View details for PubMedCentralID PMC10970487