Navigation Links
New SARS Protein Linked To Important Cell Doorway

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.

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 investiga tions 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 w hen 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.


'"/>

Source:Washington University School Of Medicine



Related biology news :

1. Quantum Dots Research Leads to New Knowledge about Protein Binding in Plants
2. Protein discovery could unlock the secret to better TB treatment
3. Researchers Uncover Key Step In Manufacture of Memory Protein
4. An HIV Protein Plays a Surprising Role in Gene Activation
5. Protein Packages Found To Activate Genes; May Be What Regulates Development And Disease
6. The Shapes Of Life: NIGMS Project Yields More Than 1,000 Protein Structures
7. PANTHER Protein Classification System Database 5.0
8. Duke Chemists Isolating Individual Molecules Of Toxic Protein In Alzheimers, Parkinsons Disease
9. Newly Discovered Compound Blocks Known Cancer-Causing Protein
10. UF Researchers Map Bacterial Proteins That Cause Tooth Loss
11. Protein offers way to stop microscopic parasites in their tracks
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:3/23/2016)... March 23, 2016 ... Sicherheit Gesichts- und Stimmerkennung mit Passwörtern ... (NASDAQ: MESG ), ein führender Anbieter ... Unternehmen mit SpeechPro zusammenarbeitet, um erstmals dessen ... wird die Möglichkeit angeboten, im Rahmen mobiler ...
(Date:3/21/2016)... March 22, 2016 Unique ... passcodes for superior security   ... provider of secure digital communications services, today announced it ... and offer enterprise customers, particularly those in the Financial ... and voice authentication within a mobile app, alongside, and ...
(Date:3/15/2016)... ALBANY, New York , March 15, 2016 ... a new market report published by Transparency Market Research "Digital ... Growth, Trends and Forecast 2015 - 2023," the global digital ... at US$ 731.9 Mn in 2014 and is forecast to ... to 2023. Growth of micro, small and medium enterprises (MSMEs) ...
Breaking Biology News(10 mins):
(Date:4/27/2016)... , ... April 27, 2016 , ... ... simultaneous preclinical PET (Positron Emission Tomography) and MRI (Magnetic Resonance Imaging) in existing ... disease and testing novel treatments in small animal subjects. Simultaneous PET/MRI imaging offers ...
(Date:4/27/2016)... ... April 27, 2016 , ... Global Stem Cells Group ... Asia-Pacific Symposium as other research and development initiatives for potential stem cell protocol management ... Global Stem Cells Group executives began meeting to establish a working agenda and foster ...
(Date:4/27/2016)... India , April 27, 2016 ... market research report with specific focus on US, ... Japan , to the healthcare business ... research library. Complete report on the ... 11 companies and supported with 282 tables and ...
(Date:4/26/2016)... ... April 26, 2016 , ... ... Arianpour has joined the company as Chief Business Officer. Arianpour, a genomics pioneer ... technologies to market, was most recently Chief Commercial Officer of Pathway Genomics. He ...
Breaking Biology Technology: