Featured Research

from universities, journals, and other organizations

New SARS Protein Linked To Important Cell Doorway

Date:
February 14, 2005
Source:
Washington University School Of Medicine
Summary:
As public health officials in China brace for a potential resurgence in SARS (Sudden Acute Respiratory Syndrome) in connection with Chinese New Year on February 9, researchers at Washington University in St. Louis have published insights into a new protein that could be an important contributor to the SARS virus' ability to cause disease and death.

Washington University researchers identified the instructions for building a potentially important protein in the genome of the SARS virus. Shown here are a diagram of the protein's structure and an image from an experiment that proved SARS makes the protein in infected cells.
Credit: Image courtesy of Washington University School Of Medicine

As public health officials in China brace for a potential resurgence in SARS (Sudden Acute Respiratory Syndrome) in connection with Chinese New Year on February 9, researchers at Washington University in St. Louis have published insights into a new protein that could be an important contributor to the SARS virus' ability to cause disease and death.

Related Articles


When the SARS virus first jumped from its still unknown animal reservoir to humans in late 2002, it caused approximately 800 deaths and 8,000 infections in several Asian countries. Months before SARS became available for direct study, Washington University researchers used the SARS genome, finished a mere half-year after the first human infections, to look for potentially important viral proteins.

As reported recently in the journal Structure, their efforts revealed orf7a, a SARS protein that makes its home in a structure cells use to modify proteins destined for transport to the cell surface. Researchers don't have any hard evidence of orf7a's function, but they speculate that the protein's positioning could enable it to block proteins that help alert the immune system or to assist reproduced viral proteins as they make their way out of the cell.

The finding exemplifies a primary directive of the University's BioMed 21 Initiative: harness the power of genetic information to rapidly advance possibilities for patient treatment. If further investigation shows orf7a is important to the SARS virus' ability to cause disease, scientists will already have much of the knowledge they need to develop ways to disable or weaken it.

"The key to studying novel viruses used to be the ability to isolate the virus and grow it in a culture," notes lead author Daved Fremont, Ph.D., assistant professor of biochemistry and molecular biophysics and of pathology and immunology. "Now we can take these viral genetic sequences, which can be attained very rapidly, and get a head start on detailed biophysical investigations of emerging diseases months before we can even begin to work with such diseases in culture."

Fremont led the initial analysis, which was dedicated to identifying sequences of genetic code that might translate into proteins that could help the virus avoid immune system attacks. He and his colleagues sought such sequences in portions of the virus' accessory genome—areas of its genetic code not commonly found in other viruses.

SARS belongs to a class of viruses known as coronaviruses. Because those viruses typically aren't harmful to humans, researchers suspect a gene in the SARS accessory genome may be providing the virus with most of its pathogenic punch.

Their computerized search highlighted a section of the SARS genetic code that shared several features with immune evasion proteins previously identified in other viruses. Some genetic codes contain sequences of protein-building instructions that the organisms never use, and the researchers had no proof yet that SARS actually made use of the sequence their analysis identified. Geneticists call such sequences of genetic information open reading frames, and the SARS sequence therefore came to be known as open reading frame 7a, or orf7a.

To produce the orf7a protein, research instructor Christopher Nelson, Ph.D., and graduate student Chung Lee, both of the Fremont laboratory, transplanted orf7a into bacteria. When the bacteria made the protein, researchers purified it and used it to determine the three-dimensional structure of orf7a. This purified protein also allowed colleague Michael Diamond, M.D., Ph.D., assistant professor of molecular microbiology, to generate orf7a-specific antibodies.

Andrew Pekosz, Ph.D., assistant professor of molecular microbiology, applied those antibodies to cell cultures infected with the SARS virus, revealing that the virus does produce the orf7a protein.

"We learned that the virus does make the protein, but we also got a big surprise when we looked at where the protein was," says Diamond. "Based on our analysis of the genome, we thought the orf7a protein would be on the surface of infected cells, decoying the immune system in some obvious way. But we found that most orf7a protein was inside the cell and little if any of it was on the surface."

Further experiments revealed that part of the protein specializes in getting orf7a to the Golgi apparatus—the structure cells use to prepare proteins for transport to the cell surface--and keeping it there.

Plans for follow-up include studies of a recently produced version of the SARS virus where orf7a has been genetically knocked out. Scientists hope to use it to learn what orf7a does for the virus and how important it is to the virus' ability to survive and reproduce.

"If knocking out orf7a significantly attenuates the virus, we may able to look at the possibility of using it to make a SARS vaccine," Pekosz speculates.

##

Nelson CA, Pekosz A, Lee CA, Diamond MS, Fremont DH. Structure and intracellular targeting of the SARS-Coronavirus Orf7a Accessory Protein. Structure, January 2005, 75-85.

Funding from the National Institutes of Health supported this research.

Washington University School of Medicine's full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked second in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.


Story Source:

The above story is based on materials provided by Washington University School Of Medicine. Note: Materials may be edited for content and length.


Cite This Page:

Washington University School Of Medicine. "New SARS Protein Linked To Important Cell Doorway." ScienceDaily. ScienceDaily, 14 February 2005. <www.sciencedaily.com/releases/2005/02/050212185849.htm>.
Washington University School Of Medicine. (2005, February 14). New SARS Protein Linked To Important Cell Doorway. ScienceDaily. Retrieved December 20, 2014 from www.sciencedaily.com/releases/2005/02/050212185849.htm
Washington University School Of Medicine. "New SARS Protein Linked To Important Cell Doorway." ScienceDaily. www.sciencedaily.com/releases/2005/02/050212185849.htm (accessed December 20, 2014).

Share This


More From ScienceDaily



More Plants & Animals News

Saturday, December 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
Monarch Butterflies Descend Upon Mexican Forest During Annual Migration

Monarch Butterflies Descend Upon Mexican Forest During Annual Migration

Reuters - Light News Video Online (Dec. 19, 2014) Millions of monarch butterflies begin to descend onto Mexico as part of their annual migration south. Rough Cut (no reporter narration) Video provided by Reuters
Powered by NewsLook.com
The Best Protein-Filled Foods to Energize You for the New Year

The Best Protein-Filled Foods to Energize You for the New Year

Buzz60 (Dec. 19, 2014) The new year is coming and nothing will energize you more for 2015 than protein-filled foods. Fitness and nutrition expert John Basedow (@JohnBasedow) gives his favorite high protein foods that will help you build muscle, lose fat and have endless energy. Video provided by Buzz60
Powered by NewsLook.com
Birds Might Be Better Meteorologists Than Us

Birds Might Be Better Meteorologists Than Us

Newsy (Dec. 19, 2014) A new study suggests a certain type of bird was able to sense a tornado outbreak that moved through the U.S. a day before it hit. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Plants & Animals

Earth & Climate

Fossils & Ruins

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins