Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Research reveals how antibodies neutralize mosquito-borne virus

03.04.2013
Researchers have learned the precise structure of the mosquito-transmitted chikungunya virus pathogen while it is bound to antibodies, showing how the infection is likely neutralized.

The findings could help researchers develop effective vaccines against the infection, which causes symptoms similar to dengue fever, followed by a prolonged disease that affects the joints and causes severe arthritis. In recent outbreaks, some cases progressed to fatal encephalitis.

The researchers studied "virus-like particles," or non-infectious forms of the virus. They also obtained near atomic-scale resolution of the virus attached to four separate antibodies.

"We knew these antibodies neutralize the real virus, so we wanted to know how they do it," said Michael Rossmann, Purdue University's Hanley Distinguished Professor of Biological Sciences.

Findings are detailed in a research paper appearing Tuesday (April 2) in the journal eLife.

The scientists used a technique called cryoelectron microscopy to uncover critical structural details about the virus-like particles bound to the antibodies. The particles are made of 180 "heterodimers," molecules made of two proteins: envelope protein 1, or E1, and envelope protein 2, or E2.
The findings show the precise structure of the virus-like particle bound to a key part of the antibodies, called the antigen binding fragment, or Fab, which attaches to the heterodimers making up the virus's outer shell. The analyses showed that the antibodies stabilize the viral surface, hindering fusion to the host cell and likely neutralizing infection.

Chikungunya is an alphavirus, a family of viruses that includes eastern equine encephalitis.

"This is the first time the structure of an alphavirus has been examined in this detail," Rossmann said.

The research is aimed at learning precisely how viruses infect humans and other hosts, knowledge that may lead to better vaccines and antiviral drugs, Rossmann said.

Chikungunya in 2005 caused an epidemic on Réunion Island. A mutation in the E1 protein has allowed the virus to replicate more efficiently, which is considered the primary reason for its recent extensive spread, infecting millions of people in Africa and Asia.
The paper was co-authored by Purdue researchers Siyang Sun and Ye Xiang, Akahata Wataru of the National Institutes of Health, Heather Holdaway of Purdue, Pankaj Pal of the Washington University School of Medicine, Xinzheng Zhang of Purdue, Michael S. Diamond of the Washington University School of Medicine, Gary J. Nabel of the NIH, and Rossmann.

The research team conducted experiments to record the structure of the virus in different orientations and obtained a three-dimensional structure with a resolution of 5.3 Ångstroms, or 5.3 ten-billionths of a meter.
The research, funded by the NIH, is ongoing and involves one graduate student and five postdoctoral students. One goal is to learn how the virus is modified when the antibodies bind to the virus and to obtain higher-resolution images.

Writer: Emil Venere, 765-494-4709, venere@purdue.edu

Source: Michael Rossmann, 765-494-4911, mgr@indiana.bio.purdue.edu
Note to Journalists: Journalists may obtain a copy of the research paper by contacting Emil Venere, 765-494-4709, venere@purdue.edu

ABSTRACT

Structural Analyses at Pseudo Atomic Resolution of Chikungunya Virus and Antibodies Show Mechanisms of Neutralization
Siyang Sun1,4, Ye Xiang1,4, Akahata Wataru2, Heather Holdaway1,5, Pankaj Pal3, Xinzheng Zhang1, Michael S. Diamond3, Gary J. Nabel2, Michael G Rossmann1,* (1 Dept of Biological Sciences, Purdue University; 2 Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health; 3 Departments of Medicine, Molecular Microbiology, Pathology & Immunology, Washington University School of Medicine; 4 These authors contributed equally to this work)

* Corresponding author. Department of Biological Sciences, 240 S. Martin Jischke Drive, Purdue University, West Lafayette, IN 47907-2032, USA. Tel.: +1 765-494-4911; Fax: +1 765-496-1189; E-mail: mr@purdue.edu

A 5.3 Å resolution, cryo-electron microscopy (cryoEM) map of Chikungunya virus-like particles (VLPs) has been interpreted using the previously published crystal structure of the Chikungunya E1-E2 glycoprotein heterodimer. The heterodimer structure was divided into domains to obtain a good fit to the cryoEM density. Differences in the T=4 quasi equivalent heterodimer components show their adaptation to different environments. The spikes on the icosahedral 3-fold axes and those in general positions are significantly different to each other, possibly representing different phases during initial generation of fusogenic E1 trimers.

CryoEM maps of neutralizing Fab fragments complexed with VLPs have been interpreted using the crystal structures of the Fab fragments and the VLP structure. Based on these analyses the CHK-152 antibody was shown to stabilize the viral surface, hindering the exposure of the fusion-loop, likely neutralizing infection by blocking fusion. The CHK-9, m10 and m242 antibodies surround the receptor-attachment site, probably inhibiting infection by blocking cell attachment.

Emil Venere | EurekAlert!
Further information:
http://www.purdue.edu

More articles from Life Sciences:

nachricht Closing the carbon loop
08.12.2016 | University of Pittsburgh

nachricht Newly discovered bacteria-binding protein in the intestine
08.12.2016 | University of Gothenburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Closing the carbon loop

08.12.2016 | Life Sciences

Applicability of dynamic facilitation theory to binary hard disk systems

08.12.2016 | Physics and Astronomy

Scientists track chemical and structural evolution of catalytic nanoparticles in 3-D

08.12.2016 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>