Featured Research

from universities, journals, and other organizations

Multitasking may be Achilles heel for hepatitis C

Date:
January 4, 2010
Source:
Rockefeller University
Summary:
Despite its tiny genome, the hepatitis C virus packs a mean punch. The virus is a microcosm of efficiency, and each of its amino acids plays multiple roles in its survival and ability to sidestep attack. But new research suggests that this fancy footwork and multitasking could be the key to bringing down the virus. The work, which focuses on a once-ignored protein, provides insights on how drug therapy for sufferers of the disease might be improved.

Despite its tiny genome, the hepatitis C virus packs a mean punch. The virus is a microcosm of efficiency, and each of its amino acids plays multiple roles in its survival and ability to sidestep attack. But new research from Rockefeller University suggests that this fancy footwork and multitasking could be the key to bringing down the virus. The work, which focuses on a once-ignored protein, provides insights on how drug therapy for sufferers of the disease might be improved.

The protein, NS2, which is one of the 10 proteins that make up the hepatitis C virus, gained momentum as a plausible drug target in 2006, when Charles M. Rice, head of the Laboratory of Virology and Infectious Disease, and his team solved the structure of its protease domain. The domain spans the second half of NS2 and acts like a molecular scissor, cleaving itself from its neighbor, NS3. (At first, the 10 proteins that make up the virus are strung together in a continuous chain, which is later cleaved by various enzymes.) By that time, it's also known to aid in the production of infectious virus particles.

Now Rice and his team have dissected the nooks and crannies of this protease domain down to the amino acids that make them up, and have mapped which amino acids are responsible for churning out infectious particles, and distinguished them from those involved in the cleaving process. During the researchers' meticulous poking and prodding, deleting and replacing, one amino acid in particular caught their attention: the protein's very last one.

"When we changed or deleted the terminal leucine -- leucine 217 -- infectious virus production shut down," says graduate student Thomas Dentzer, who led the research. "But what really intrigued us was leucine 217's position."

After the protease makes its cut, leucine 217 remains in a protein fold that makes up the protease's active site. Although the active site isn't involved in making infectious virus particles, Dentzer and Rice -- who is also Maurice R. and Corinne P. Greenberg Professor in Virology and scientific director of the Center for the Study of Hepatitis C at Rockefeller -- showed that it is essential for the protease's cleaving activity. With both functions mapping to this tiny region of NS2, the researchers suggest that drugs targeting this area might be able to pack a double punch against the virus.

Since the hepatitis C virus has an uncanny ability to mutate and evade detection just when the body's immune forces are closing in, punching several phases of the virus's life cycle simultaneously may be a better approach than dealing one phase a forceful blow. "A double punch may give the immune system time to attack the virus before it mutates," says Dentzer. "So this is a good therapeutic target to explore."

The fact that this amino acid is exposed on the virus's surface makes the finding all the more exciting and suggests that it is involved in protein-protein interactions during the life cycle of the virus. "We not only have a target that can weaken the virus, but a target that is also accessible," says Rice. "It is a lead that can really help us move forward.


Story Source:

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


Journal Reference:

  1. Dentzer et al. Determinants of the Hepatitis C Virus Nonstructural Protein 2 Protease Domain Required for Production of Infectious Virus. Journal of Virology, 2009; 83 (24): 12702 DOI: 10.1128/JVI.01184-09

Cite This Page:

Rockefeller University. "Multitasking may be Achilles heel for hepatitis C." ScienceDaily. ScienceDaily, 4 January 2010. <www.sciencedaily.com/releases/2009/12/091231153631.htm>.
Rockefeller University. (2010, January 4). Multitasking may be Achilles heel for hepatitis C. ScienceDaily. Retrieved September 15, 2014 from www.sciencedaily.com/releases/2009/12/091231153631.htm
Rockefeller University. "Multitasking may be Achilles heel for hepatitis C." ScienceDaily. www.sciencedaily.com/releases/2009/12/091231153631.htm (accessed September 15, 2014).

Share This



More Health & Medicine News

Monday, September 15, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

EU Ministers and Experts Meet to Discuss Ebola Reponse

EU Ministers and Experts Meet to Discuss Ebola Reponse

AFP (Sep. 15, 2014) The European Commission met on Monday to coordinate aid that the EU can offer to African countries affected by the Ebola outbreak. Duration: 00:58 Video provided by AFP
Powered by NewsLook.com
Despite The Risks, Antibiotics Still Overprescribed For Kids

Despite The Risks, Antibiotics Still Overprescribed For Kids

Newsy (Sep. 15, 2014) A new study finds children are prescribed antibiotics twice as often as is necessary. Video provided by Newsy
Powered by NewsLook.com
FDA Eyes Skin Shocks Used at Mass. School

FDA Eyes Skin Shocks Used at Mass. School

AP (Sep. 15, 2014) The FDA is considering whether to ban devices used by the Judge Rotenberg Educational Center in Canton, Massachusetts, the only place in the country known to use electrical skin shocks as aversive conditioning for aggressive patients. (Sept. 15) Video provided by AP
Powered by NewsLook.com
Respiratory Virus Spreads To Northeast, Now In 21 States

Respiratory Virus Spreads To Northeast, Now In 21 States

Newsy (Sep. 14, 2014) The respiratory virus Enterovirus D68, which targets children, has spread from the Midwest to 21 states. 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:
from the past week

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