While the hepatitis C virus can infect chimpanzees and humans, scientists have been unable to study the progression of the virus' life cycle or possible treatments in small animal models. The new mouse model is the first to be developed with a fully functioning immune system.
"Our genetically humanized mouse model for hepatitis C will allow us to gain deeper insights in the biology of this important pathogen," says senior author Alexander Ploss, a research assistant professor at Rockefeller. "This robust small animal model also has the potential to serve a critical role in testing and prioritizing drug and vaccine candidates. Results from these tests can potentially guide more expensive pre-clinical and clinical studies in higher order organisms, including humans."
The development of this mouse model is the culmination of several years of research by scientists in the laboratory of Charles M. Rice and other research groups. In 2006, Rice and his colleagues were the first to successfully create a strain of hepatitis C in the laboratory, which can efficiently be grown in the laboratory, and is also infectious in animals. More recently, Rice, Ploss and their colleagues discovered that hepatitis C virus infection requires previously identified CD81 and scavenger receptor type B class I, as well as two tight junction molecules, claudin 1 and occludin. The Rockefeller researchers showed that human CD81 and occludin were required for hepatitis C virus to enter mouse cells.
In the new study, the Rockefeller researchers and colleagues at The Scripps Research Institute tested whether introducing some of these previously identified human genes into mice would allow them to infect the animals with the hepatitis C virus. The researchers compared two groups of mice: one group expressed two genes, CD81 and occludin, while mice in the second group were normal. They found that expression of human CD81 and human occludin in the mouse liver rendered the animals susceptible to HCV infection. Ploss and his colleagues also developed a novel reporter system, which allowed them to sensitively detect HCV infection in living animals.
"We have established a precedent for applying mouse genetics to dissect viral entry and validate the role of scavenger receptor type B class 1, a molecule that is being considered as a novel antiviral drug target, for HCV uptake in a living animal," says Charles M. Rice, Maurice R. and Corinne P. Greenberg Professor and head of the Laboratory of Virology and Infectious Disease at Rockefeller. Rice also is executive and scientific director of the Center for the Study of Hepatitis C, an interdisciplinary center established jointly by The Rockefeller University, NewYork-Presbyterian Hospital and Weill Cornell Medical College.
Worldwide at least 130 million people are chronically infected with HCV, which poses a risk of severe liver injury and liver cancer. Current treatments are only partially effective and have considerable side effects, and a vaccine against hepatitis C does not exist.
"The global HCV epidemic mandates the development of more effective therapeutics including a vaccine," says Ploss. "This mouse model is a first step toward a platform that effectively serves this purpose."
This research was supported in part by the National Institutes of Health.
Joseph Bonner | EurekAlert!
Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München
Second research flight into zero gravity
21.10.2016 | Universität Zürich
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.
In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...
'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.
Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
21.10.2016 | Health and Medicine
21.10.2016 | Information Technology
21.10.2016 | Materials Sciences