GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE347nnn/GSE347489/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE347489GEOGSEfalseSingle-dose peripheral therapy with the neutralizing human monoclonal antibody A6 reverses neuroinflammatory and antiviral gene expression in the brains of Australian bat lyssavirus-infected miceRabies is a fatal viral encephalitis caused by most or all known members of the lyssavirus genus, and no therapy is known to prevent mortality once lyssavirus has entered the human CNS. We have previously shown that a single peripheral dose of a neutralizing human monoclonal antibody (mAb) can protect mice from fatal lyssavirus infection even when delivered after CNS invasion. To determine how such therapy alters the biology of established CNS infection, mice were mock-infected or infected in the footpad with Australian bat lyssavirus expressing luciferase (ABLV-Luc) and then treated on day 5 post-infection with a single 10 mg/kg intraperitoneal dose of either the neutralizing human mAb A6 or the irrelevant-specificity control human mAb m102.4. Whole brains were harvested at day 14 post-infection and total RNA sequencing was performed. Principal component analysis separated m102.4-treated infected animals from both mock-infected controls and A6-treated infected animals, with A6-treated samples clustering closely with mock-infected controls. Infection in the presence of the control mAb induced broad upregulation of interferon-stimulated, antiviral, chemokine and inflammatory genes (e.g. Ifit1, Zbp1, Mx1, Isg15, Cxcl10, Ccl2, Ccl5, Tnf, Il12b, Cfb), whereas A6-treated animals showed few differentially expressed genes relative to mock-infected controls. Gene set enrichment analysis confirmed strong enrichment of inflammatory and antiviral pathways in m102.4-treated animals relative to both other groups. These data demonstrate that peripheral single-dose therapy with a neutralizing mAb broadly reduces expression of neuroinflammatory mediators during the acute phase of CNS-resident lyssavirus infection.2026/09/22GSE347489GSM10054123GSM10054122GSM10054121GSM10054120GSM10054127GSM10054126GSM10054125GSM10054124GSM10054119GSM10054118GSM10054117GSM1005412824247347489Mus musculus[42758862]