Navigation Links
Synthetic virus supports a bat origin for SARS
Date:11/25/2008

SARS severe acute respiratory syndrome alarmed the world five years ago as the first global pandemic of the 21st century. The coronavirus (SARS-CoV) that sickened more than 8,000 people and killed nearly 800 of them may have originated in bats, but the actual animal source is not known.

In an effort to understand how SARS-CoV may have jumped from bats to humans, a team of investigators from Vanderbilt University Medical Center and the University of North Carolina at Chapel Hill has now generated a synthetic SARS-like bat coronavirus. The virus the largest replicating synthetic organism ever made is infectious in cultured cells and mice, the researchers report in the Proceedings of the National Academy of Sciences.

The findings identify pathways by which a bat coronavirus may have adapted to infect humans. The studies also provide a model approach for rapid identification, analysis and public health responses to future natural or intentional virus epidemics.

Zoonotic viruses animal pathogens that can cause disease in humans pose a serious threat to public health, said Mark Denison, M.D., professor of Pediatrics at Vanderbilt and a co-leader of the research with Ralph Baric, Ph.D., professor of Epidemiology at UNC.

"It's becoming more and more clear that new human epidemics will continue to originate in animals," said Denison, who is also an associate professor of Microbiology & Immunology. "However, the mechanisms of trans-species movement and adaptation of viruses from animals to humans remain poorly understood."

At the time of the SARS epidemic, the culprit virus was rapidly identified as a coronavirus (SARS-CoV). But it didn't look like the two human coronaviruses that were known, which cause 20 percent to 30 percent of common colds, and the animal "reservoir" (the original animal host for the virus) remained elusive.

Investigators became convinced that bats were the likely source, but bat coronaviruses had never been successfully grown in culture or animals, which blocked studies of replication, evolution and prevention.

The Denison and Baric teams, with lead authors Michelle Becker, Ph.D., of Vanderbilt, and Rachel Graham Ph.D., of UNC, determined that not being able to grow the virus represented a critical gap in the ability to rapidly identify and respond to new pathogens.

To address this vulnerability, the team decided to use synthetic biology to recover a non-cultivatable virus.

"The idea is, here's the virus, or the virus group, that we think became SARS-CoV," Denison said. "Let's see if we can synthetically recover the bat virus and test it in cultured cells and in animal models let the bat virus show us the pathways that it may have used to become a human pathogen.

"Then we would have a viable candidate virus to test for diagnostics, vaccines and treatment."

The investigators used published SARS-like bat coronavirus sequences to establish a "consensus" genome sequence "the best bet for a virus genome that would be viable," Denison said. They then used commercial DNA synthesis and reverse genetics to "build" the consensus viral genome and several variations.

The consensus synthetic SARS-like bat CoV did not initially grow in culture. But substitution of a single small region from human SARS-CoV the Spike protein receptor binding domain that is critical for viral entry into human cells allowed the new chimeric SARS-like bat CoV to grow well in monkey cells (commonly used to study human SARS-CoV).

"It was a tremendous surprise that such a small region of SARS-CoV was sufficient to allow the bat virus to move from zero growth to very efficient growth in cells," Denison said.

The chimeric virus also grew well in mouse cells modified to express the receptor for SARS-CoV and in primary human airway epithelial cells. It grew poorly in mice, but a single additional change in the Spike region allowed efficient growth in mice, without causing a SARS-like disease.

The studies suggest that a very simple recombination event may have been enough to allow a coronavirus to move from one species to another, Denison said, adding that "after a virus gains the capacity to jump species, additional simple adaptations may be adequate to increase its ability to grow in the new animal host."

At all stages of design and implementation, the Vanderbilt and UNC teams acknowledged potential safety concerns and encouraged ongoing external safety reviews. Research with all bat viruses even weakened mutants was performed under the same stringent biosafety conditions used to study virulent SARS-CoV. The investigators found that human antibodies known to render SARS-CoV noninfectious also neutralized the bat SARS-like coronavirus, providing an additional safety measure.

"The approaches used here address fundamental questions in virus movement between species," Denison said, "and also could improve public health preparedness by allowing rapid responses to naturally emerging or intentionally introduced zoonotic pathogens."


'/>"/>

Contact: John Howser
john.howser@vanderbilt.edu
615-322-4747
Vanderbilt University Medical Center
Source:Eurekalert

Related biology news :

1. Chloroplast f and m Thioredoxins Discovered in Nonphotosynthetic Tissues
2. Synthetic compound promotes death of lung-cancer cells, tumors
3. Experts from Stevens, Merck, publish joint paper, Biosynthetic Studies of Platensimycin
4. Researchers decode genetics of rare photosynthetic bacteria
5. Researchers decode genetics of rare photosynthetic bacterium
6. Synthetic molecules may be less expensive alternative to therapeutic antibodies, researchers find
7. Berkeley researchers identify photosynthetic dimmer switch
8. Oregano oil works as well as synthetic insecticides to tackle common beetle pest
9. New projects to raise UK profile in synthetic biology
10. Synthetic Biology: funders move to address social and ethical challenges
11. Synthetic cocoa chemical slows growth of tumors in human cell lines
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/24/2016)... Ampronix facilitates superior patient care by providing unparalleled technology to leaders of ... the latest premium product recently added to the range of products distributed by Ampronix. ... ... ... Medical Display- Ampronix News ...
(Date:5/3/2016)... VILNIUS, Lithuania , May 3, 2016 /PRNewswire/ ... today released the MegaMatcher Automated Biometric Identification ... deployment of large-scale multi-biometric projects. MegaMatcher ABIS can ... and accuracy using any combination of fingerprint, face ... of MegaMatcher SDK and MegaMatcher ...
(Date:4/19/2016)... The new GEZE SecuLogic access ... "all-in-one" system solution for all door components. It can ... door interface with integration authorization management system, and thus ... minimal dimensions of the access control and the optimum ... offer considerable freedom of design with regard to the ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... ... 2016 , ... Supplyframe, the Industry Network for electronics hardware ... . Located in Pasadena, Calif., the Design Lab’s mission is to bring together ... built and brought to market. , The Design Lab is Supplyframe’s physical representation ...
(Date:6/23/2016)... 2016  Blueprint Bio, a company dedicated to identifying, ... community, has closed its Series A funding round, according ... "We have received a commitment from Forentis Fund ... to meet our current goals," stated Matthew Nunez ... to complete validation on the current projects in our ...
(Date:6/23/2016)... ... June 23, 2016 , ... Regulatory Compliance Associates® Inc. (RCA), ... free webinar on Performing Quality Investigations: Getting to Root Cause. ... no charge. , Incomplete investigations are still a major concern to the Regulatory ...
(Date:6/22/2016)... , June 22, 2016 Cell ... will allow them to produce up to one ... one lot within one week. These high-quality, consistent ... laboriously preparing cells and spend more time doing ... through a proprietary, high-volume manufacturing process that produces ...
Breaking Biology Technology: