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From Guardian to Gateway: B cell receptor-dependent enhancement (BDE) of dengue virus infection in dengue-reactive B cells
Gebo, Chad
Gebo, Chad
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2026-02-18
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Dengue virus (DENV) is the causative agent of dengue, a mosquito-borne disease that is responsible for approximately 400 million infections every year. One of the defining features of dengue is immune-mediated enhancement. The leading mechanistic explanation for this phenomenon is antibody dependent enhancement (ADE). Multiple independent groups have shown that B cells are the largest reservoir of virally infected cells in circulation during acute dengue and have been shown to be poorly susceptible to infection through conventional means or ADE. In this thesis, we characterize a novel mechanism of DENV entry into specific subsets of B cells via the B cell receptor (BCR), known as BCR-dependent enhancement (BDE). We show that expression of a DENV-reactive BCR can render a cell susceptible to infection and that the pool of susceptible B cells increases following primary exposure to DENV. We also show that DENV entry into cells via this mechanism requires early, proximal BCR signaling and leads to productive DENV infection. These findings, alongside ADE, work to fill in mechanistic gaps within the model of ADE and have implications in the establishment of infection during secondary disease as well as identify insights into potential mechanisms of DENV immunopathogenesis.
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