The related report by Lázaro et al, "Hepatitis C virus replication in transfected and serum-infected cultured human fetal hepatocytes," appears in the February issue of The American Journal of Pathology.
Hepatitis C virus (HCV) infection affects approximately 170,000,000 people worldwide. HCV liver disease, which may induce liver inflammation, cirrhosis, and/or hepatocellular carcinoma, represents the foremost reason for liver transplantation in much of the U.S.
Study of HCV replication within liver cells, or hepatocytes, has been hampered by a lack of adequate virus culture systems. Some systems allow the virus to infect cells but do not permit prolonged replication and production of virus, while other systems rely on derivatives of permissive virus isolates for efficient replication in transformed (mutated) cell lines. Still lacking has been a system to sustain replication of novel virus isolates from patients using nontransformed hepatocytes.
Nelson Fausto of the University of Washington School of Medicine has crossed this hurdle using a human fetal hepatocyte culture system that was previously developed in his lab. Using this system, his group has demonstrated sustained replication and production of virus particles for at least 2 months, with these virus particles able to infect new cells.
In their first experiments, Fausto and colleagues transfected hepatocyte cultures with HCV genomic RNA and found replication of HCV RNA genomes and production of core protein (for virus particle formation). Release of infectious virus particles was confirmed, as media from these cells were able to infect naive hepatocytes. Finally, virus particles were examined by electron microscopy and shown to possess the expected size and shape of HCV virus particles.
Once the system was established, the group examined whether sera from patients carrying HCV could infect the human fetal hepatocytes. When sera from patients infected with different HCV strains were added to the hepatocyte culture system, viral replication occurred and new virus particles were produced.
In both transfection and infection models, virus particles were released in a cyclical manner, with bursts of virus produced every 10-14 days. This is similar to what has been reported during clinical HCV infection, possibly due to the host's natural defenses. Interestingly, cultured hepatocytes responded to viral replication by displaying signs of distress and cell death and by expressing interferon-beta, a cellular antiviral, in an effort to control the infection.
This culture system provides a breakthrough in studying HCV replication in nontransformed hepatocytes, the natural target of the virus. By allowing infection by patient serum containing a wide array of virus strains, this system may allow better understanding of the differences between different strains, further improving treatment strategies.
Audra Cox | EurekAlert!
Polymers Based on Boron?
18.01.2018 | Julius-Maximilians-Universität Würzburg
Bioengineered soft microfibers improve T-cell production
18.01.2018 | Columbia University School of Engineering and Applied Science
What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...
For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.
Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...
At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.
No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...
Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.
Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...
The oceans are the largest global heat reservoir. As a result of man-made global warming, the temperature in the global climate system increases; around 90% of...
08.01.2018 | Event News
11.12.2017 | Event News
08.12.2017 | Event News
18.01.2018 | Life Sciences
18.01.2018 | Life Sciences
18.01.2018 | Earth Sciences