Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Discovery Could Lead to a New Animal Model for Hepatitis C

30.01.2009
Rockefeller University scientists have identified a protein that allows the hepatitis C virus to enter mouse cells, a finding that represents the clearest path yet for developing a much-needed vaccine as well as tailored treatments for the 170 million people across the globe living with the tenacious, insidious and rapidly changing virus.

During its career, the potentially fatal hepatitis C virus has banked its success on a rather unusual strategy: its limitations.

Its inability to infect animals other than humans and chimpanzees has severely hampered scientists in developing a useful small animal model for the disease.

But now, in a breakthrough to be published in the January 29 advance online issue of Nature, Rockefeller University scientists have identified a protein that allows the virus to enter mouse cells, a finding that represents the clearest path yet for developing a much-needed vaccine as well as tailored treatments for the 170 million people across the globe living with the tenacious, insidious and rapidly changing virus.

By using a genetic screen, the group, led by Charles M. Rice, head of the Laboratory of Virology and Infectious Disease, identified a human protein, called occludin, that makes mouse cells susceptible to the virus. The discovery means that scientists now have the complete list of cellular factors — a total of four — that are required for the virus to enter nonhuman cells.

The hepatitis C virus exclusively targets human liver cells, suggesting that these cells express genes that allow uptake of the virus, genes that are not expressed in other human and nonhuman cells, explains Rice. In past years, three proteins — CD81, CLDN1 and SR-BI — were identified as having key roles in shuttling the virus into cells, but something was clearly missing. Rice's group found that even when they engineered mouse cells to overexpress all three proteins, the cells still denied the virus entry.

The discovery of occludin, however, has changed that. When Rice and his colleagues engineered mouse and human cell lines to express all four proteins, they showed that each cell line became infectible with the virus. To further establish occludin's role as a required entry factor, the group showed that human liver cells naturally express high levels of occludin, and that by silencing its expression, they could give these once highly susceptible liver cells the ability to completely block infection.

"You know, you sort of have to get lucky," says Rice, who is also Maurice R. and Corinne P. Greenberg Professor at Rockefeller. "You've got these three factors you know are important, but you could have 10 other human factors that could have been necessary for hepatitis C virus entry. This work shows that's not the case."

In their DNA screen, the team, including Alexander Ploss, a research associate in the lab, and Matthew J. Evans, currently at Mount Sinai School of Medicine in New York, first cloned all the genes that were expressed in liver cells and then delivered them to mouse cells. "Then, going through an iterative screening process, we honed in on the genes that made the mouse cells permissive," says Ploss, who spearheaded the project with Evans.

Since mice and humans each have a species-specific version of the four factors, the group used hamster cells to see which combination of factors did the best job at making the cells infectible. They found that in the case of two of the proteins, occludin and CD81, only the human versions worked; for SR-BI and CLDN1, the human and mouse versions did an equally good job. These experiments not only suggest that there may be more than one potential animal model, but also that there are several specific combinations of entry factors that could generate them.

"This work provides a clear foundation upon which we can now begin to construct an animal model for the uniquely human pathogen," says Rice. "This is only a first step but in terms of creating an animal model for hepatitis C, it's a big leap forward."

Thania Benios | Newswise Science News
Further information:
http://www.rockefeller.edu

More articles from Life Sciences:

nachricht Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY

nachricht NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Future electronic components to be printed like newspapers

A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.

The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

A smart safe rechargeable zinc ion battery based on sol-gel transition electrolytes

20.07.2018 | Power and Electrical Engineering

Reversing cause and effect is no trouble for quantum computers

20.07.2018 | Information Technology

Princeton-UPenn research team finds physics treasure hidden in a wallpaper pattern

20.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>