Fig. 4: VLDLR is crucial for SFV neuroinvasion from the circulation.

Immunofluorescence staining for VLDLR in the choroid plexus of Vldlr KO (a) and B6129SF2/J (Vldlr wild-type control mouse) mice (b). No VLDLR can be detected in Vldlr KO sample. CSF: cerebrospinal fluid. c Kaplan–Meier analysis of Vldlr KO mice infected intravenously (IV) with 1 × 10⁶ PFU SFV4 or SFV4(A774st) and B6129SF2/J infected intravenously (IV) with 1 × 10⁶ PFU SFV4(A774st). Statistical analysis done with log-rank test. Data from two independent experiments. Representative immunostaining for SFV proteins in Vldlr KO (d) and B6129SF2/J (e) mouse brain at day 4 after 1 × 10⁶ PFU IV SFV4(A774st) injection. f, g Analysis of virus in different brain regions, blood and CSF with plaque titration (PFU/ml). Samples from 5 Vldlr KO mice collected at d2, 3, and 4 after 1 × 10⁶ PFU (red circles) IV injection of SFV4(A774st). Additional CSF samples analyzed at d3 after 1 × 10⁷ PFU injection (gray dots). ND: not detected. g plaque titration of brain samples collected from B6129SF2/J mice at d4 after 1 × 10⁷ PFU SFV4(A774st) injection. Limit of detection: 50 PFU/ml. Each data point represents the result from an individual mouse. h Kaplan–Meier analysis of Vldlr KO mice infected intracranially (IC) or intranasally (IN) SFV4(A774st). All mice succumb to neurological symptoms. Data from two independent experiments. i Representative immunostaining of Vldlr KO mouse olfactory epithelium (OE) 2 days after IN SFV4(A774st) injection. SFV staining can be seen at the surface layer of epithelium (indicated with arrow) but also in deeper tissues. j Representative immunostaining of Vldlr KO mouse brain (transverse plane) 4 days after IN SFV4(A774st) injection. SFV staining can be seen in olfactory bulb but also in deeper in the brain tissues. Experiments done with 7–10 week-old female mice. Source data for (c, f, g, h) and P values for (c) are provided as a Source Data file.