TRANSCRIPTOMIC AND FUNCTIONAL PATHWAY ANALYSIS OF ZIKA VIRUS-INDUCED PARALYSIS AND RECOVERY IN A MOUSE MODEL OF GUILLAIN-BARRÉ SYNDROME

Abstract

We analyze how transcriptional programs shift from paralysis to recovery in a ZIKV-linked GBS mouse model using spinal-cord RNA-seq from sham, paralyzed, and recovering groups. Public reads (PRJNA1144966/SRP524499) were QC’d (FastQC/MultiQC), trimmed (Trim Galore; Phred ≥30; length ≥70 bp), then aligned to mouse GRCm39 with STAR; counts by featureCounts; Ensembl release 109; CPM normalization. edgeR quasi-likelihood contrasts (Paralyzed vs Sham; Recovering vs Paralyzed; Recovering vs Sham), thresholds FDR ≤0.05 and |log₂FC| ≥1; PCA showed clear stage separation (one sham outlier on PC2 retained). In paralysis, interferon/NF-κB immune mediators (e.g., TNF, IFIT1, ISG15, OASL2, STAT1, CXCL10) are up, while ribosomal/splicing genes are down; recovery attenuates inflammatory signatures and re-expresses neuronal programs. Paralysis enriches immune/viral response; recovering vs paralyzed enriches axonogenesis/synaptic organization; recovering vs sham retains antigen-receptor/immune-synapse signals. GSEA: strong positive enrichment for interferon/NF-κB in paralysis; neurotrophin/cell-adhesion modules in recovery. Paralysis: KEGG/Reactome cytokines, chemokines, complement, FcR→NF-κB/MAPK; Recovery: shift toward GPCR-linked and synaptic signaling, indicating an immune-to-neural transition. A two-phase trajectory emerges: immune injury → resolution/remodeling. Candidate markers: acute (IFIT1, ISG15, CXCL10, STAT1, TNF), resolution (ARG1, MSR1, CLEC4N, IFI30, TGM2), adaptive recovery (PDCD1, CTLA4, CXCR3, CCL5, IL12B, ITGAE). The study outlines a coherent neuroimmune progression from antiviral/inflammatory activation to reparative neuronal remodeling, proposing phase-specific transcriptional signatures for monitoring and potential therapeutic timing.