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 email@example.com or Ryan A. Garcia at (979) 845-9237 or firstname.lastname@example.org
Ryan Garcia | EurekAlert!
Routing gene therapy directly into the brain
07.12.2017 | Boston Children's Hospital
New Hope for Cancer Therapies: Targeted Monitoring may help Improve Tumor Treatment
01.12.2017 | Berliner Institut für Gesundheitsforschung / Berlin Institute of Health (BIH)
Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.
To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...
The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.
Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...
With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong
Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...
An interdisciplinary group of researchers interfaced individual bacteria with a computer to build a hybrid bio-digital circuit - Study published in Nature Communications
Scientists at the Institute of Science and Technology Austria (IST Austria) have managed to control the behavior of individual bacteria by connecting them to a...
Physicists in the Laboratory for Attosecond Physics (run jointly by LMU Munich and the Max Planck Institute for Quantum Optics) have developed an attosecond electron microscope that allows them to visualize the dispersion of light in time and space, and observe the motions of electrons in atoms.
The most basic of all physical interactions in nature is that between light and matter. This interaction takes place in attosecond times (i.e. billionths of a...
08.12.2017 | Event News
07.12.2017 | Event News
05.12.2017 | Event News
11.12.2017 | Physics and Astronomy
11.12.2017 | Materials Sciences
11.12.2017 | Earth Sciences