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Updated: Jun 17, 2026
A Murine Model of Dengue Virus-induced Acute Viral Encephalitis-like Disease
Published on: April 28, 2019
Immature dengue virus: a veiled pathogen?
Izabela A Rodenhuis-Zybert1, Hilde M van der Schaar, Júlia M da Silva Voorham
1Department of Medical Microbiology, Molecular Virology Section, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands.
Abstract:
Cells infected with dengue virus release a high proportion of immature prM-containing virions. In accordance, substantial levels of prM antibodies are found in sera of infected humans. Furthermore, it has been recently described that the rates of prM antibody responses are significantly higher in patients with secondary infection compared to those with primary infection. This suggests that immature dengue virus may play a role in disease pathogenesis. Interestingly, however, numerous functional studies have revealed that immature particles lack the ability to infect cells. In this report, we show that fully immature dengue particles become highly infectious upon interaction with prM antibodies. We demonstrate that prM antibodies facilitate efficient binding and cell entry of immature particles into Fc-receptor-expressing cells. In addition, enzymatic activity of furin is critical to render the internalized immature virus infectious. Together, these data suggest that during a secondary infection or primary infection of infants born to dengue-immune mothers, immature particles have the potential to be highly infectious and hence may contribute to the development of severe disease.
Insights
Immature dengue virus particles become infectious when they interact with prM antibodies, potentially contributing to severe dengue disease during secondary infections. This interaction enhances cell entry and infectivity.
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Dengue virus-infected cells release immature virions containing prM proteins.
- Elevated prM antibody levels are observed in infected individuals, particularly during secondary infections.
- Immature dengue virus particles are generally considered non-infectious.
Purpose of the Study:
- To investigate the role of prM antibodies in the infectivity of immature dengue virus particles.
- To elucidate the mechanisms by which immature dengue virus contributes to disease pathogenesis.
Main Methods:
- Assessing the infectivity of immature dengue virus particles after interaction with prM antibodies.
- Analyzing the role of Fc-receptor-expressing cells in immature virion entry.
- Investigating the necessity of furin enzymatic activity for viral maturation and infectivity.
Main Results:
- Fully immature dengue virus particles gain significant infectivity upon binding with prM antibodies.
- prM antibodies facilitate the efficient entry of immature virions into Fc-receptor-expressing cells.
- Furin enzymatic activity is crucial for processing internalized immature virions into infectious forms.
Conclusions:
- Immature dengue virus particles can become highly infectious in the presence of prM antibodies.
- This mechanism may contribute to severe dengue pathogenesis, especially during secondary infections or in specific primary infection scenarios.
- Understanding this pathway offers insights into dengue disease progression and potential therapeutic targets.
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