News Release

Penn study identifies how ebola virus avoids the immune system

Peer-Reviewed Publication

University of Pennsylvania School of Medicine

How Ebola Virus Avoids the Immune System

image: Scanning electron microscope image of Ebola virions (spaghetti-like filaments) on the surface of a tetherin-expressing cell (center). The other three cells seen in this image (upper right and upper and lower left) do not have the filamentous virus on their surfaces. view more 

Credit: Paul Bates, Ph.D., University of Pennsylvania School of Medicine

PHILADELPHIA, PA - Researchers at the University of Pennsylvania School of Medicine have likely found one reason why the Ebola virus is such a powerful, deadly, and effective virus. Using a cell culture model for Ebola virus infection, they have discovered that the virus disables a cellular protein called tetherin that normally can block the spread of virus from cell to cell.

"Tetherin represents a new class of cellular factors that possess a very different means of inhibiting viral replication," says study author Paul Bates, PhD, Associate Professor of Microbiology at the University of Pennsylvania School of Medicine. "Tetherin is the first example of a protein that affects the virus replication cycle after the virus is fully made and prevents the virus from being able to go off and infect the next cell." These findings appear online this week in the Proceedings of the National Academy of Sciences.

When a cell is infected with a virus like Ebola, which is deadly to 90 percent of people infected, the cell is pirated by the virus and turned into a production factory that makes massive quantities on new virions. These virions are then released from that cell to infect other cells and promote the spreading infection.

Tetherin is one of the immune system's responses to a viral infection. If working properly, tetherin stops the infected cell from releasing the newly made virus, thus shutting down spread to other cells. However, this study shows that the Ebola virus has developed a way to disable tetherin, thus blocking the body's response and allowing the virus to spread.

"This information gives us a new way to study how tetherin works," says Bates. "Binding of a protein produced by Ebola to tetherin apparently inactivates this cellular factor. Understanding how the Ebola protein blocks the activity of tetherin may facilitate the design of therapeutics to inhibit this interaction, allowing the cell's natural defense systems to slow down viral replication and give the animal or person a chance to mount an effective antiviral response and recover."

Previous research had found that tetherin plays a role in the immune system's response to HIV-1, a retrovirus, and that tetherin is also disabled by HIV. These new studies reveal that human cells also use this defense against other types of viruses, such as Ebola, that are not closely related to HIV-1. "Because we see such broad classes of viruses that are affected by tetherin, it's possible that all enveloped viruses are targets of this antiviral system," says Bates. "If so, then understanding how tetherin works and how viruses escape from the effect of tetherin will be very important."

###

Rachel L. Kaletsky, Joseph R. Francica and Caroline Agrawal-Gamse of the University of Pennsylvania School of Medicine are co-authors of this study. This work was funded by the Public Health Service Grants and the Philip Morris External Research Foundation.

This release and a related image can be found at: http://www.uphs.upenn.edu/news/News_Releases/2009/01/tetherin-ebola.html

PENN Medicine is a $3.6 billion enterprise dedicated to the related missions of medical education, biomedical research, and excellence in patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.

Penn's School of Medicine is currently ranked #4 in the nation in U.S.News & World Report's survey of top research-oriented medical schools; and, according to most recent data from the National Institutes of Health, received over $379 million in NIH research funds in the 2006 fiscal year. Supporting 1,700 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.

The University of Pennsylvania Health System (UPHS) includes its flagship hospital, the Hospital of the University of Pennsylvania, rated one of the nation's top ten "Honor Roll" hospitals by U.S.News & World Report; Pennsylvania Hospital, the nation's first hospital; and Penn Presbyterian Medical Center. In addition UPHS includes a primary-care provider network; a faculty practice plan; home care, hospice, and nursing home; three multispecialty satellite facilities; as well as the Penn Medicine at Rittenhouse campus, which offers comprehensive inpatient rehabilitation facilities and outpatient services in multiple specialties.


Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.