A5062982193- Mosquito-borne diseases and control
- Bacteriophages and microbial interactions
- Viral Infections and Vectors
- Cytomegalovirus and herpesvirus research
- RNA and protein synthesis mechanisms
- Genomics and Phylogenetic Studies
- Insect symbiosis and bacterial influences
- Bacterial Genetics and Biotechnology
- Advanced Electron Microscopy Techniques and Applications
- Enzyme Structure and Function
- Viral Infections and Outbreaks Research
- Protein Structure and Dynamics
- Plant Virus Research Studies
- Genetics, Bioinformatics, and Biomedical Research
- Virus-based gene therapy research
- Malaria Research and Control
- Vector-borne infectious diseases
- Biosensors and Analytical Detection
- Virology and Viral Diseases
- Viral gastroenteritis research and epidemiology
- Microbial Community Ecology and Physiology
- Enzyme Production and Characterization
- Vibrio bacteria research studies
- Cancer Research and Treatments
- Animal Virus Infections Studies
National University of Singapore
2013-2024
Duke-NUS Medical School
2010-2020
Purdue University West Lafayette
1999-2009
State Street (United States)
2003-2009
Institut de Biologia Molecular de Barcelona
2008
Osaka University
2008
University of Basel
2005
University of Glasgow
2005
Rutherford Appleton Laboratory
2005
Laboratoire de Cristallographie et Sciences des Matériaux
2005
There are four closely-related dengue virus (DENV) serotypes. Infection with one serotype generates antibodies that may cross-react and enhance infection other serotypes in a secondary infection. We demonstrated DENV 2 (DENV2)-specific human monoclonal antibody (HMAb) 2D22 is therapeutic mouse model of antibody-enhanced severe disease. determined the cryo-electron microscopy (cryo-EM) structures HMAb complexed two different DENV2 strains. binds across viral envelope (E) proteins dimeric...
Abstract Dengue virus (DENV) infects ~400 million people annually. There is no licensed vaccine or therapeutic drug. Only a small fraction of the total DENV-specific antibodies in naturally occurring dengue infection consists highly neutralizing antibodies. Here we show that human monoclonal antibody 5J7 exceptionally potent, 50% at nanogram-range concentration. The 9 Å resolution cryo-electron microscopy structure Fab 5J7–DENV complex shows single molecule binds across three envelope...
Mimivirus is the largest known virus whose genome and physical size are comparable to some small bacteria, blurring boundary between a cell. Structural studies of have been difficult because its long surface fibers. Here we report use enzymatic digestions remove fibers in order expose viral capsid. Cryo-electron microscopy (cryoEM) atomic force were able show that 20 icosahedral faces capsids hexagonal arrays depressions. Each depression surrounded by six trimeric capsomers similar structure...
The mechanism of action a serotype-specific natural human antibody against dengue virus has been identified.
ABSTRACT Previous binding studies of antibodies that recognized a partially or fully hidden epitope suggest insect cell-derived dengue virus undergoes structural changes at an elevated temperature. This was confirmed by our cryo-electron microscopy images incubated 37°C, where viruses change their surface from smooth to rough. Here we present the structures 37°C. Image analysis showed four classes particles. The three-dimensional (3D) map one these classes, representing half imaged...
Research Article14 January 2014Open Access A potent anti-dengue human antibody preferentially recognizes the conformation of E protein monomers assembled on virus surface Guntur Fibriansah Program in Emerging Infectious Diseases, Duke–NUS Graduate Medical School, Singapore City, Centre for BioImaging Sciences, National University Singapore, Search more papers by this author Joanne L Tan Scott Smith Department Medicine, Vanderbilt University, Nashville, TN, USA The Vaccine Center, Adamberage...
Dengue virus is a major human pathogen that has four serotypes (DENV1 to -4). Here we report the cryoelectron microscopy (cryo-EM) structures of immature and mature DENV1 at 6- 4.5-Å resolution, respectively. The subnanometer-resolution maps allow accurate placement all surface proteins. Although viruses showed vastly different protein organizations, envelope transmembrane (E-TM) regions remain in similar positions. pivotal role E-TM leads identification start end positions proteins during...
Abstract Structures of flavivirus (dengue virus and Zika virus) particles are known to near-atomic resolution show detailed structure arrangement their surface proteins (E prM in immature or M mature virus). By contrast, the capsid proteins:RNA complex, which forms core particle, is poorly understood, likely due inherent dynamics. Here, we stabilize via an antibody that binds across E proteins, resulting a subnanometer within particle. Fitting protein into densities shows presence helix...
Abstract The rapid spread of Zika virus (ZIKV), which causes microcephaly and Guillain-Barré syndrome, signals an urgency to identify therapeutics. Recent efforts rescreen dengue human antibodies for ZIKV cross-neutralization activity showed antibody C10 as one the most potent. To investigate ability block fusion, we determined cryoEM structures C10-ZIKV complex at pH levels mimicking extracellular (pH8.0), early (pH6.5) late endosomal (pH5.0) environments. 4.0 Å resolution pH8.0 structure...
Abstract Dengue virus infection can cause dengue hemorrhagic fever (DHF). NS1 is multifunctional. The intracellular dimeric (iNS1) forms part of the viral replication complex. Previous studies suggest extracellular secreted (sNS1), which a major factor contributing to DHF, exists as hexamers. structure iNS1 well-characterised but not that sNS1. Here we show by cryoEM recombinant sNS1 in multiple oligomeric states: tetrameric (stable and loose conformation) hexameric structures. Stability...
Dengue virus (DENV), a mosquito-borne virus, is responsible for millions of cases infections worldwide. There are four DENV serotypes (DENV1 to -4). After primary infection, the antibodies elicited confer lifetime protection against that serotype. However, in secondary infection with another serotype, preexisting may cause antibody-dependent enhancement (ADE) macrophage cells, leading development more severe form disease, dengue hemorrhagic fever. Thus, safe vaccine should stimulate all...
Dengue virus infects approximately 100 million people annually, but there is no available therapeutic treatment. The mimetic peptide, DN59, consists of residues corresponding to the membrane interacting, amphipathic stem region dengue envelope (E) glycoprotein. This peptide inhibitory all four serotypes virus, as well other flaviviruses. Cryo-electron microscopy image reconstruction particles incubated with DN59 showed that were largely empty, concurrent formation holes at five-fold...
Significance Chikungunya virus (CHIKV) is a significant human pathogen that causes debilitating and long-lasting arthritis. Currently, there no approved vaccine or specific therapeutic. We show two highly potent anti-CHIKV antibodies—CHK-124 CHK-263—can inhibit multiple steps of the CHIKV infection cycle determined their cryogenic electron microscopy structures in complex with particles to 4- 5-Å resolution. describe structural details epitopes CHK-124 CHK-263 how they relate functional...
Although many viruses are icosahedral when they initially bind to one or more receptor molecules on the cell surface, such an interaction is asymmetric, probably causing a breakdown in symmetry and conformation of original infecting virion preparation for membrane penetration release viral genome. Cryoelectron microscopy biochemical analyses show that transferrin receptor, cellular canine parvovirus, can only few 60 icosahedrally equivalent sites virion, indicating either parvovirus has...