Whole-brain transcriptional responses to wild-type and attenuated G(K245E) Australian bat lyssavirus in mice

ABSTRACT: A spontaneously arising variant of luciferase-expressing Australian bat lyssavirus (ABLV-Luc) carrying a single point mutation in the viral glycoprotein gene, G(K245E), was identified in a passage 9 viral stock and found to be non-lethal in mice. Although in vivo infection with ABLV-Luc-WT and ABLV-Luc-G(K245E) followed similar anatomical progression and kinetics, the intensity of viral transcription in the spinal cord and brain, the manifestation of disease signs and the magnitude of weight loss were all reduced for the G(K245E) mutant, and all G(K245E)-infected animals survived. To determine whether abrogation of inflammatory and antiviral gene expression is required for protection from lyssavirus-induced mortality, total RNA sequencing was performed on whole brains harvested at day 14 post-infection from mice that were mock-infected or infected with ABLV-Luc-WT or ABLV-Luc-G(K245E). Principal component analysis separated both infected groups from mock-infected controls along PC1 (88% of variance), and both infected groups displayed robust induction of antiviral and inflammatory genes, with a high degree of overlap in enriched pathways. Direct comparison of ABLV-Luc-WT with ABLV-Luc-G(K245E) revealed only modest gene expression differences, though interferon and inflammatory response pathways were more strongly enriched in the WT group. These data indicate that the magnitude of inflammatory and antiviral gene expression in the brain is generally proportional to viral load, and that a robust neuroinflammatory response to ABLV does not by itself predict mortality.

ORGANISM(S): Mus musculus

PROVIDER: GSE347494 | GEO | 2026/09/22

REPOSITORIES: GEO