The system, Chen explains, enables researchers to study the effects of molecules that obstruct all aspects of the hepatitis C virus (HCV) life cycle. That's a significant milestone in HCV research, says Chen, noting that previous methods of developing drug treatments for the virus have been limited by the fact that researchers were only able to study one aspect of the HCV life cycle. Chen's findings appear in the most recent edition of the scientific journal Proceedings of the National Academy of Sciences.
First identified in 1989 and responsible for hepatitis C, an infectious disease affecting the liver, HCV has infected an estimated 180 million people worldwide. Spread by blood-to-blood contact, HCV can cause chronic infection that leads to dangerous scarring of the liver, liver failure, liver cancer and death.
Although new infections resulting from blood transfusions are rare thanks to screening measures that began in 1990, the overall number of people facing death or serious liver disease from HCV is steadily rising because people often live decades with the virus before showing symptoms, Chen says. In addition, injection drug users are at high risk for infection from contaminated needles.
The only existing therapy for HCV is a physically and emotionally taxing 48-week course of treatment that cures less than half of all patients who undergo it, Chen says. The particularly grueling nature of the treatment – it's been compared to chemotherapy – as well as the high financial costs associated with it often result in many patients opting to forego the therapy.
Because Chen's newly developed screening system enables the discovery of small, low-cost molecules that block the HCV life cycle, she believes it could contribute to new, more affordable and more effective therapies for hepatitis C.
The screening system uses an innovative way to "see" cells that are infected with HCV.
"Typically when a virus infects a cell, it's not obvious to detect; it's not easy to distinguish an infected cell from an uninfected cell," Chen says. "Much in the same way a person who is infected with HCV does not initially feel anything, when a cell is initially infected nothing really observable happens. This makes it difficult to distinguish HCV infection in cells."
To address this challenge, Chen "tweaked" the cells she was studying by inserting a gene into them that triggers cell death if HCV enters that cell. This allowed Chen to easily measure the extent of infection in her genetically engineered cells by quantifying the degree of cell death within the cell cultures she was examining.
These engineered cells were grown in miniature compartments in the presence of infectious HCV, and a different chemical was added to each compartment.
"We could then look and see which cells were able to survive because if you have chemicals that don't inhibit HCV, the cells will die, but if you have a molecule that blocks the HCV life cycle, the cells will grow," Chen says. "And because we were able to look at the complete life cycle of the virus with our system, we discovered inhibitors of the virus across three different stages: entry into cells, reproduction within cells, and final escape from infected cells to attack new cells."
Testing about 1,000 different chemicals, Chen found several that strongly inhibited the HCV life cycle. Some of the inhibitors, she said, obstruct virus entry into a cell. Others inhibit virus replication, meaning that infected cells won't be able to support the reproduction and growth of the virus as much. Chen also found effective inhibitors that keep the virus from escaping the cell even if it grows well inside the cell.
"Since this virus changes all of the time, you really want to hit it across multiple aspects simultaneously," Chen says. "Nevertheless, most current efforts to block the HCV life cycle focus only on its replication within cells due to the long-time absence of a system that allows for convenient screening of molecules blocking other aspects of the virus' life cycle such as entry into cells and release from cells.
"Our system is well-suited to large-scale drug screening efforts because the technology is simple to use and can be easily scaled up to test extremely large collections of compounds using a robotic system," Chen says. "We anticipate that this system will enable the discovery of many more new and more potent HCV antivirals."
Working with Chen to develop the system were Karuppiah Chockalingam and Rudo Simeon, postdoctoral associate and graduate student, respectively, from Texas A&M and Charles Rice, professor from Rockefeller University.
About research at Texas A&M University: As one of the world's leading research institutions, Texas A&M is in the vanguard in making significant contributions to the storehouse of knowledge, including that of science and technology. Research conducted at Texas A&M represents an annual investment of more than $582 million, which ranks third nationally for universities without a medical school, and underwrites approximately 3,500 sponsored projects. That research creates new knowledge that provides basic, fundamental and applied contributions resulting in many cases in economic benefits to the state, nation and world.
Contact: Zhilei Chen at (979) 862-1610 or firstname.lastname@example.org or Ryan A. Garcia at (979) 845-9237 or email@example.com
Ryan Garcia | EurekAlert!
Researchers release the brakes on the immune system
18.10.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn
Norovirus evades immune system by hiding out in rare gut cells
12.10.2017 | University of Pennsylvania School of Medicine
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
19.10.2017 | Physics and Astronomy
19.10.2017 | Physics and Astronomy
19.10.2017 | Life Sciences