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 Identifying drug targets for leukaemia
02.05.2016 | The Hong Kong Polytechnic University

nachricht A cell senses its own curves: New research from the MBL Whitman Center
29.04.2016 | Marine Biological Laboratory

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: 2+1 is Not Always 3 - In the microworld unity is not always strength

If a person pushes a broken-down car alone, there is a certain effect. If another person helps, the result is the sum of their efforts. If two micro-particles are pushing another microparticle, however, the resulting effect may not necessarily be the sum their efforts. A recent study published in Nature Communications, measured this odd effect that scientists call “many body.”

In the microscopic world, where the modern miniaturized machines at the new frontiers of technology operate, as long as we are in the presence of two...

Im Focus: Tiny microbots that can clean up water

Researchers from the Max Planck Institute Stuttgart have developed self-propelled tiny ‘microbots’ that can remove lead or organic pollution from contaminated water.

Working with colleagues in Barcelona and Singapore, Samuel Sánchez’s group used graphene oxide to make their microscale motors, which are able to adsorb lead...

Im Focus: ORNL researchers discover new state of water molecule

Neutron scattering and computational modeling have revealed unique and unexpected behavior of water molecules under extreme confinement that is unmatched by any known gas, liquid or solid states.

In a paper published in Physical Review Letters, researchers at the Department of Energy's Oak Ridge National Laboratory describe a new tunneling state of...

Im Focus: Bionic Lightweight Design researchers of the Alfred Wegener Institute at Hannover Messe 2016

Honeycomb structures as the basic building block for industrial applications presented using holo pyramid

Researchers of the Alfred Wegener Institute (AWI) will introduce their latest developments in the field of bionic lightweight design at Hannover Messe from 25...

Im Focus: New world record for fullerene-free polymer solar cells

Polymer solar cells can be even cheaper and more reliable thanks to a breakthrough by scientists at Linköping University and the Chinese Academy of Sciences (CAS). This work is about avoiding costly and unstable fullerenes.

Polymer solar cells can be even cheaper and more reliable thanks to a breakthrough by scientists at Linköping University and the Chinese Academy of Sciences...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

The “AC21 International Forum 2016” is About to Begin

27.04.2016 | Event News

Soft switching combines efficiency and improved electro-magnetic compatibility

15.04.2016 | Event News

Grid-Supportive Buildings Give Boost to Renewable Energy Integration

12.04.2016 | Event News

 
Latest News

Identifying drug targets for leukaemia

02.05.2016 | Life Sciences

Clay nanotube-biopolymer composite scaffolds for tissue engineering

02.05.2016 | Materials Sciences

NASA's Fermi Telescope helps link cosmic neutrino to blazar blast

02.05.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>