ArticleJournal of virology2011
A single amino acid in nonstructural protein NS4B confers virulence to dengue virus in AG129 mice through enhancement of viral RNA synthesis.
Article in Journal of virology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 84 citations in OpenAlex.
- Targeting a genomic RNA G-quadruplex of dengue virus with small molecules as an alternative to protein-targeted therapeutics.Journal of biomedical science · 2026Article
- Aged AG129 mice support the generation of highly virulent novel mouse-adapted DENV (1-4) viruses exhibiting neuropathogenesis and high lethality.Virus research · 2024Article
- Development in the Inhibition of Dengue Proteases as Drug Targets.Current medicinal chemistry · 2024Review
- Introduction to West Nile Virus.Methods in molecular biology (Clifton, N.J.) · 2023Article
- A nonstructural protein 1 capture enzyme-linked immunosorbent assay specific for dengue viruses.PloS one · 2023Article
- Development and characterization of an animal model of Japanese encephalitis virus infection in adolescent C57BL/6 mouse.Disease models & mechanisms · 2021Article
- Relative contribution of nonstructural protein 1 in dengue pathogenesis.The Journal of experimental medicine · 2020Article
- Article
- Insight into the Tropism of Dengue Virus in Humans.Viruses · 2019Review
- RIG-I Activation by a Designer Short RNA Ligand Protects Human Immune Cells against Dengue Virus Infection without Causing Cytotoxicity.Journal of virology · 2019Article
- Dengue Virus Infection Activates Interleukin-1β to Induce Tissue Injury and Vascular Leakage.Frontiers in microbiology · 2019Article
- Using a Virion Assembly-Defective Dengue Virus as a Vaccine Approach.Journal of virology · 2018Article
- Article
- Neutralization of antibody-enhanced dengue infection by VIS513, a pan serotype reactive monoclonal antibody targeting domain III of the dengue E protein.PLoS neglected tropical diseases · 2018Article
- Dengue vaccine-induced CD8+ T cell immunity confers protection in the context of enhancing, interfering maternal antibodies.JCI insight · 2017Article
- Understanding Zika Virus Stability and Developing a Chimeric Vaccine through Functional Analysis.mBio · 2017Article
- Dengue Virus Reporter Replicon is a Valuable Tool for Antiviral Drug Discovery and Analysis of Virus Replication Mechanisms.Viruses · 2016Review
- Maternal Antibody-Mediated Disease Enhancement in Type I Interferon-Deficient Mice Leads to Lethal Disease Associated with Liver Damage.PLoS neglected tropical diseases · 2016Article
- An Overview of Current Approaches Toward the Treatment and Prevention of West Nile Virus Infection.Methods in molecular biology (Clifton, N.J.) · 2016Article
- Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dengue (DEN) is a mosquito-borne viral disease that has become an increasing economic and health burden for the tropical and subtropical world. The lack of an appropriate animal model of DEN has greatly impeded the study of its pathogenesis and the development of vaccines/antivirals. We recently reported a DEN virus 2 (DENV-2) strain (D2Y98P) that lethally infects immunocompromised AG129 mice, resulting in organ damage or dysfunction and increased vascular permeability, hallmarks of severe DEN in patients (G. K. Tan et al., PLoS Negl. Trop. Dis. 4:e672, 2010). Here we report the identification of one critical virulence determinant of strain D2Y98P. By mutagenesis, we showed that a Phe-to-Leu alteration at amino acid position 52 in nonstructural protein NS4B completely abolished the pathogenicity of the D2Y98P virus, as evidenced by a lack of lethality and the absence of histological signs of disease, which correlated with reduced viral titers and intact vascular permeability. Conversely, a Leu-to-Phe alteration at position 52 of NS4B in nonvirulent DENV-2 strain TSV01 led to 80% lethality and increased viremia. The NS4B(Phe52) viruses displayed enhanced RNA synthesis in mammalian cells but not in mosquito cells. The increased viral RNA synthesis was independent of the ability of NS4B to interfere with the host type I interferon response. Overall, our results demonstrate that Phe at position 52 in NS4B confers virulence in mice on two independent DENV-2 strains through enhancement of viral RNA synthesis. In addition to providing further insights into the functional role of NS4B protein, our findings further support a direct relationship between viral loads and DEN pathogenesis in vivo, consistent with observations in DEN patients.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.