English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Recent clinical studies have revealed that severe symptoms of dengue fever are associated with low pre-existing antibody levels. These findings provide direct clinical evidence for the theory of antibody-dependent enhancement of infection (ADE), which postulates that sub-neutralizing levels of antibodies facilitate the invasion of host cells by the dengue virus. Here, we carried out molecular simulations guided by previous  in vitro  experiments and structural studies to explore the role of antibody fine-specificity, viral conformation, and maturation state—key aspects of dengue virology that are difficult to manipulate experimentally—on ADE in the context of primary and secondary infections. Our simulation results reproduced  in vitro  studies of ADE, providing a molecular basis for how sub-neutralizing antibody concentrations can enhance infection. We found that antibody fine specificity, or the relative antibody response to different epitopes on the surface of the dengue virus, plays a major role in determining the degree of ADE observed at low antibody concentrations. Specifically, we found that the higher the relative antibody response to certain cross-reactive epitopes, such as the fusion loop or prM, the greater was the range of antibody concentrations where ADE occurred, providing a basis for why low antibody concentrations are associated with severe dengue disease in secondary infections. Furthermore, we found that partially mature viral states, in particular, are associated with the greatest degree of ADE.

frontiers in cellular and infection microbiology

Molecular Simulations Reveal the Role of Antibody Fine Specificity and Viral Maturation State on Antibody-Dependent Enhancement of Infection in Dengue Virus