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 Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory

nachricht How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>