Dengue disease is caused by four different flavivirus serotypes, which infect 390 million people yearly with 25% symptomatic cases and for which no licensed vaccine is available. Recent phase III vaccine trials showed partial protection, and in particular no protection for dengue virus serotype 2 (refs 3, 4). Structural studies so far have characterized only epitopes recognized by serotype-specific human antibodies. We recently isolated human antibodies potently neutralizing all four dengue virus serotypes. Here we describe the X-ray structures of four of these broadly neutralizing antibodies in complex with the envelope glycoprotein E from dengue virus serotype 2, revealing that the recognition determinants are at a serotype-invariant site at the E-dimer interface, including the exposed main chain of the E fusion loop and the two conserved glycan chains. This 'E-dimer-dependent epitope' is also the binding site for the viral glycoprotein prM during virus maturation in the secretory pathway of the infected cell, explaining its conservation across serotypes and highlighting an Achilles' heel of the virus with respect to antibody neutralization. These findings will be instrumental for devising novel immunogens to protect simultaneously against all four serotypes of dengue virus.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1038/nature14130 | DOI Listing |
mSphere
December 2024
Australian Infectious Disease Research Centre, School of Biological Sciences, The University of Queensland, Brisbane, Queensland, Australia.
Vigilin is a large and evolutionary conserved RNA-binding protein (RBP), which can interact with RNA through its KH domain. Vigilin is, therefore, a multifunctional protein reported to be associated with RNA transport and metabolism, sterol metabolism, chromosome segregation, carcinogenesis, and heterochromatin-mediated gene silencing. The receptor for activated C kinase 1 (RACK1) is another highly conserved protein involved in many cellular pathways.
View Article and Find Full Text PDFCureus
November 2024
Internal Medicine, Al Qassimi Hospital, Sharjah, ARE.
Dengue fever, caused by the dengue virus and transmitted by mosquitoes, poses a significant global health threat, particularly in tropical and subtropical regions. Severe cases can manifest as dengue hemorrhagic fever (DHF) or dengue shock syndrome, leading to complications such as plasma leakage, fluid accumulation, respiratory distress, severe bleeding, and organ impairment. Among these complications, gastrointestinal (GI) bleeding is particularly concerning due to its potential to rapidly deteriorate the patient's condition.
View Article and Find Full Text PDFDengue virus (DENV) is an increasingly important human pathogen, with already half of the globe's population living in environments with transmission potential. Since only a minority of cases are captured by direct detection methods (RT-PCR or antigen tests), serological assays play an important role in the diagnostic process. However, individual assays can suffer from low sensitivity and specificity and interpreting results from multiple assays remains challenging, particularly because interpretations from multiple assays may differ, creating uncertainty over how to generate finalized interpretations.
View Article and Find Full Text PDFClin Rheumatol
December 2024
Department of Medicine, University of Otago, Wellington, New Zealand.
Climate change and pollution are a major existential threat. Healthcare contributes a noteworthy 4-6% to the total carbon footprint and 5-7% of the total greenhouse gas (GHG) emissions. Environmental pollution and modern lifestyles are also contributing to the increased prevalence of autoimmune and lifestyle-related rheumatic disease.
View Article and Find Full Text PDFVirus Res
December 2024
Department of Translational Virology, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth (Deemed to be University), Katraj-Dhankawadi, Pune 411043, India. Electronic address:
Platelets are essential for hemostasis and vascular integrity. Platelets recognize dengue virus through the DC-SIGN receptor. Upon pathogen recognition, platelets rapidly modulate the expression of adhesion molecules to trigger immune cell interactions and regulate the immune response.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!