Mechanistic insights into Bluetongue virus immunodynamics: a Bayesian within-host modelling approach.

Abstract

Bluetongue virus (BTV) is a vector-transmitted orbivirus that infects ruminant livestock and wildlife, causing substantial economic losses owing to its impact on animal health and trade. Despite extensive study, the mechanisms underlying infection and immune dynamics remain unclear. Here, we develop and calibrate a mechanistic within-host model of BTV infection in experimentally infected sheep to quantify the contributions of innate and adaptive immune responses to viral control. The model integrates longitudinal data on viral RNA dynamics reverse transcriptase quantitative polymerase chain reaction, CD8+ T-cell and antibody dynamics, and midge infection outcomes within a Bayesian inference framework using Hamiltonian Monte Carlo. Our results reveal that CD8+ T lymphocytes mediate over 90% of viral clearance, establishing them as the primary drivers of disease control. Interferons exert an early but moderate antiviral effect, whereas antibodies contribute minimally to acute clearance yet sustain long-term immunity. Sensitivity analyses identify viral replication and infection rates as key determinants of peak viral RNA load. Collectively, these findings provide a quantitative framework linking immune kinetics, viral dynamics and transmission potential, advancing mechanistic understanding of BTV pathogenesis, and informing strategies for vaccine and antiviral development in ruminant hosts.