Biology subjects

Ganasarajah, A.

Publications and source records attributed to Ganasarajah, A..

3 recordsLinked to original sources

bioRxiv2026

Myeloperoxidase (MPO) exacerbates dengue-associated liver injury and contributes to disease pathogenesis in mouse models

Severe dengue can damage the liver through unestablished mechanisms. We investigated the role of myeloperoxidase (MPO), a neutrophil enzyme, in dengue through patients, fatal liver samples, and mouse infection models. Observations from two independent clinical cohorts revealed elevated plasma MPO levels in dengue and, in one cohort, MPO was further linked to liver injury markers during the critical phase of disease, whereas livers from dengue fatal cases revealed MPO build-up in the vicinity of CD177+ activated neutrophils. In mice, dengue led to MPO overexpression, oxidative damage, and broad activation of innate and systemic inflammatory pathways in livers. Blocking MPO activity alleviated these and improved survival in one model and delayed disease progression without preventing death in another. These findings establish MPO as a functional mediator of severe dengue-associated liver injury and inflammation, which warrants further preclinical investigation into its hepatic pathogenic mechanism and its validity as target for therapeutic intervention.

pathology↗

bioRxiv2026

Nanoluciferase reporter preserves immunocompetent glioma model fidelity while facilitating longitudinal molecular imaging

Glioblastoma studies employ syngeneic orthotopic models to preserve tumor-immune interactions, but intracranial tumor burden is challenging to monitor longitudinally. Bioluminescence imaging enables non-invasive assessment, although reporter immunogenicity may compromise model fidelity. We engineered murine GL261 glioma cells to stably express nanoluciferase (NLuc) and compared them with parental GL261 (WT) and GL261 cells expressing red-shifted firefly luciferase (Red-FLuc). In vitro, GL261-NLuc retained growth kinetics and morphology comparable to GL261-WT and produced >100-fold stronger bioluminescence than GL261-Red-FLuc. In immunocompetent mice, GL261-NLuc formed lethal brain tumors with survival and tumor histopathology, immune profile, and response patterns to experimental oncolytic virus therapy broadly resembling GL261-WT. In contrast, GL261-Red-FLuc tumors regressed and exhibited heightened inflammation and increased infiltration of activated CD8+ T-cells. Longitudinal imaging of GL261-NLuc tumors detected treatment-associated changes in growth kinetics not captured by survival alone. These establish GL261-NLuc as a practical reporter for longitudinal immunocompetent glioblastoma studies amenable to immunotherapy evaluations.

molecular biology↗

bioRxiv2026

Haemagglutinin 162-164 deletions enhance influenza B/Victoria virus fitness and virulence in vivo

Influenza B viruses cause substantial respiratory disease and seasonal outbreaks. Despite decades of circulation in humans, only the B/Victoria lineage persisted after the COVID-19 pandemic. Continual evolution has generated hemagglutinin deletion variants at residues 162-164 that drive successive epidemics, yet their functional consequences remain poorly understood. Using integrated phylodynamics and reverse genetics, we show that Clade V1A.1 viruses carrying a two-amino acid deletion exhibit enhanced replication and increased virulence compared with ancestral viruses lacking deletions. The recently prevailing Clade V1A.3, which harbors a three-amino acid deletion together with the K136E substitution, has completely displaced V1A.1 and causes more severe disease in mice. Both clades bound efficiently to alpha 2-3 and 2-6 sialylated glycans and exhibited broad tolerance to acidic pH and elevated temperatures. These findings reveal that specific combinations of HA deletions and substitutions confer pronounced fitness advantages to emerging variants, driving global selective sweeps, evolutionary success and long-term persistence of B/Victoria lineage, and posing challenges for vaccine efficacy and influenza control.

microbiology↗