Worldwide, 185 million people have chronic hepatitis C. Since the late 1980s, when scientists discovered the virus that causes the infection, they have struggled to find ways to grow it in human cells in the lab -- an essential part of learning how the virus works and developing new effective treatments.
In a study published in Nature on August 12, scientists led by The Rockefeller University's Charles M. Rice, Maurice R. and Corinne P. Greenberg Professor in Virology and head of the Laboratory of Virology and Infectious Disease, report that when they overexpressed a particular gene in human liver cancer cell lines, the virus could easily replicate. This discovery allows study of naturally occurring forms of hepatitis C virus (HCV) in the lab.
Researchers engineered cultured cells to contain a red marker that moves into the nucleus upon HCV infection. Nothing happened when normal cells were exposed to HCV (top), but when the researchers expressed the protein SEC14L2, some nuclei changed color from blue to purple (bottom).
Credit: Laboratory of Virology and Infectious Disease at The Rockefeller University/Nature
"Being able to easily culture HCV in the lab has many important implications for basic science research," says Rice. "There is still much we don't understand about how the virus operates, and how it interacts with liver cells and the immune system. "
Scientists have long attempted to understand what makes HCV tick, and in 1999 a group of German scientists succeeded in coaxing modified forms of the virus to replicate in cells in the laboratory. However, it was soon discovered that these forms of the virus were able to replicate because they had acquired certain "adaptive" mutations.
This was true for the vast majority of all samples from patients, except one, and left scientists with a puzzling question for more than a decade: What prevents non-mutated HCV from replicating in laboratory-grown cell lines? Rice and colleagues hypothesized that one or more critical elements might be missing in these cell lines.
To test this idea, they screened a library of about 7,000 human genes to look for one whose expression would allow replication of non-mutated HCV. When the scientists expressed the gene SEC14L2, the virus replicated in its wild-type, non-mutated form. Even adding serum samples from HCV-infected patients to these engineered cell lines resulted in virus replication.
"Practically speaking, this means that if scientists want to study HCV from an infected patient, it's now possible to take a blood sample, inoculate the engineered cells, and grow that patient's form of the virus in the lab," says first author Mohsan Saeed, a postdoc in Rice's laboratory.
It's not entirely clear how the protein expressed by SEC14L2 works, says Saeed, but it appears to inhibit lipids from interacting with dangerous reactive oxygen species, a process that prevents HCV replication.
Recent advances in HCV treatment have made it possible for millions of people to be cured of the virus. "New therapies, however, are extremely expensive and not perfect," Saeed notes. "As more patients are treated, drug resistant forms of HCV are emerging. Having a cell culture system where patient isolates can be grown and tested for resistance or susceptibility to alternative antiviral drug combinations should be useful for optimizing re-treatment strategies for those that fail treatment."
Even though effective therapies for HCV do exist, there is still much we need to understand about the virus, adds Saeed -- and understanding how HCV interacts with its host cell can help scientists learn more about similar viruses for which effective treatments have yet to be developed. "The lessons learned from one disease can be true for other diseases as well," he observes.
Wynne Parry | EurekAlert!
Shipment tracking for "fat parcels" in the body
14.10.2019 | Rheinische Friedrich-Wilhelms-Universität Bonn
Antibody-based eye drops show promise for treating dry eye disease
14.10.2019 | University of Illinois at Chicago
A new research project at the TH Mittelhessen focusses on the development of a novel light weight design concept for leisure boats and yachts. Professor Stephan Marzi from the THM Institute of Mechanics and Materials collaborates with Krake Catamarane, which is a shipyard located in Apolda, Thuringia.
The project is set up in an international cooperation with Professor Anders Biel from Karlstad University in Sweden and the Swedish company Lamera from...
Superconductivity has fascinated scientists for many years since it offers the potential to revolutionize current technologies. Materials only become superconductors - meaning that electrons can travel in them with no resistance - at very low temperatures. These days, this unique zero resistance superconductivity is commonly found in a number of technologies, such as magnetic resonance imaging (MRI).
Future technologies, however, will harness the total synchrony of electronic behavior in superconductors - a property called the phase. There is currently a...
How do some neutron stars become the strongest magnets in the Universe? A German-British team of astrophysicists has found a possible answer to the question of how these so-called magnetars form. Researchers from Heidelberg, Garching, and Oxford used large computer simulations to demonstrate how the merger of two stars creates strong magnetic fields. If such stars explode in supernovae, magnetars could result.
How Do the Strongest Magnets in the Universe Form?
A hot, molten Earth would be around 5% larger than its solid counterpart. This is the result of a study led by researchers at the University of Bern. The difference between molten and solid rocky planets is important for the search of Earth-like worlds beyond our Solar System and the understanding of Earth itself.
Rocky exoplanets that are around Earth-size are comparatively small, which makes them incredibly difficult to detect and characterise using telescopes. What...
Scientists at the Max Planck Institute for Chemical Physics of Solids in Dresden, Princeton University, the University of Illinois at Urbana-Champaign, and the University of the Chinese Academy of Sciences have spotted a famously elusive particle: The axion – first predicted 42 years ago as an elementary particle in extensions of the standard model of particle physics.
The team found signatures of axion particles composed of Weyl-type electrons (Weyl fermions) in the correlated Weyl semimetal (TaSe₄)₂I. At room temperature,...
02.10.2019 | Event News
02.10.2019 | Event News
19.09.2019 | Event News
14.10.2019 | Physics and Astronomy
14.10.2019 | Earth Sciences
14.10.2019 | Health and Medicine