Navigation Links
Penn scientists find a protein that inhibits Ebola from reaching out to infect neighboring cells
Date:3/4/2008

PHILADELPHIA - Scientists at the University of Pennsylvania School of Veterinary Medicine have identified a protein, ISG15, that inhibits the Ebola virus from budding, the process by which viruses escape from cells and spread to infect neighboring cells. This study shows for the first time how ISG15 slows the spread of Ebola virus budding, an observation that could help explain how ISG15 successfully inhibits other viruses, including HIV-1 and herpes simplex virus type I. The findings, reported in the current issue of the Proceedings of the National Academy of Sciences, offer the promise of future treatments for Ebola outbreaks that now prove fatal for as many as 90 percent of victims.

According to the Penn Vet research team, ISG15 inhibits budding in an indirect way, by blocking the behavior of a particular host cell protein which is used by Ebola and other viruses to efficiently escape from cells. ISG15 specifically inhibits the host protein, Nedd4, used by the viral protein VP40 to escape from cells and allow for virus spread.

Inhibit the proteins used by a virus to reproduce and you are inhibiting the virus itself, Ronald Harty, lead author of the study and associate professor in the Department of Pathobiology at Penn Vet, said. Without host Nedd4, the Ebola virus still buds and attacks, but it doesnt bud as well. The long-term goal of our research is to understand the interplay between host and virus, with the hope of creating an anti-viral drug or inhibitor, much like how Tamiflu doesnt cure the flu but slows down the viral process, Harty said. The drug would be designed to dampen or slow down viral budding to allow an infected persons immune system to fight back.

The Ebola virus VP40 protein is the key player in the process of virus assembly and release from infected cells. VP40 buds from mammalian cells independent of other viral proteins, and efficient release of VP40 virus-like particles, VLPs, requires interactions with host proteins such as tsg101 and Nedd4, an E3 ubiquitin ligase. Ubiquitin itself is thought to be exploited by Ebola virus to facilitate efficient virus egress.

The study showed that expression of free ISG15, or the ISGylation System, UbE1L and UbcH8, inhibits budding of Ebola virus VP40 VLPs. Addressing the molecular mechanism of this inhibition, the researchers demonstrated that ISG15 interacts with Nedd4 ubiquitin ligase and inhibits ubiquitination of VP40, thus blocking budding of VP40 VLPs. These data provide evidence of antiviral activity of ISG15 against Ebola virus and suggest a mechanism of action involving disruption of Nedd4 function and subsequent ubiquitination of VP40.

This newest study has extended the teams knowledge of the reproductive process of Ebola and other viruses with similar reproductive mechanisms. Prior research by Harty and his team had shown that a sequence of four amino acids in VP40 was critical to the spread of the Ebola virus. VP40 appeared to be the necessary protein component to begin the viral budding process. The findings allowed researchers to target VP40 as a key to viral reproduction.

Penn researchers performed this research using only the VP40 protein found in the Ebola and other viruses. VP40 is not harmful in vitro, yet forms a virus-like particle, a unique phenomenon that allows for study of viral behavior without the danger associated with the virus.


'/>"/>

Contact: Jordan Reese
jreese@upenn.edu
215-573-6604
University of Pennsylvania
Source:Eurekalert

Related medicine news :

1. New prion protein discovered by Canadian scientists may offer insight into mad cow disease
2. Scientists Probe Sepsis Deadly Secrets
3. Scientists puzzled by severe allergic reaction to cancer drug in the middle Southern US
4. Scientists Develop Natural Protection for Stored Foods
5. Scientists detect presence of marburg virus in african fruit bats
6. Scientists Spot Brains Free Will Center
7. Scientists ID Likely Culprit in Popcorn Lung
8. Scientists explain how insulin secreting cells maintain their glucose sensitivity
9. Scripps Research scientists shed new light on how antibodies fight HIV
10. Scientists, physicians present latest findings in personalized cancer treatment and prevention
11. Scientists demonstate link between genetic variant and effectiveness of smoking cessation meds
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... ... 2017 , ... As health professionals work to improve their approach to healthcare, ... doing more than filling out a survey; in many cases health professionals and patients ... health care and research on the importance of active engagement with patients and members ...
(Date:10/13/2017)... ... 2017 , ... PurhealthRX , a leading Health and Nutrition Company, is ... to full spectrum CBD oil will revolutionize the rapidly growing CBD market by reducing ... easily incorporated into liquid products, while reducing costs to end users. , The team ...
(Date:10/13/2017)... , ... October 13, 2017 , ... Many families have ... many long-term care insurance companies have a waiver for care if the client has ... period, when the family pays for care, is often waived, so the benefits from ...
(Date:10/13/2017)... ... October 13, 2017 , ... Yisrayl Hawkins, Pastor and Overseer ... one of the most popular and least understood books in the Holy Scriptures, Revelation. ... descriptions that have baffled scholars for centuries. Many have tossed it off as mere ...
(Date:10/13/2017)... ... ... “America On The Brink”: the Christian history of the United States and the ... published author, William Nowers. Captain Nowers and his wife, Millie, have six children, ... in the Navy. Following his career as a naval aviator and carrier pilot, ...
Breaking Medicine News(10 mins):
(Date:10/11/2017)... Oct. 11, 2017  True Health, a leader ... its effort during National Breast Cancer Awareness month ... risks. Research ... calculated that more than 10 million American women ... in BRCA1 or BRCA2 and have not had testing. ...
(Date:10/5/2017)... 2017  In response to the nationwide opioid ... Surgeons (AAOMS) released prescribing recommendations that urge ibuprofen ... as a first-line therapy to manage a patient,s ... Recognizing the value and importance of ... Prescribing: Acute and Postoperative Pain Management" stresses that ...
(Date:10/2/2017)... 2017  Eli Lilly and Company (NYSE: ... third quarter of 2017 on Tuesday, October 24, 2017. ... day with the investment community and media to further ... call will begin at 9 a.m. Eastern time. Investors, ... webcast of the conference call through a link that ...
Breaking Medicine Technology: