The system, the researcher Zhilei Chen explains, enables scientists to study the effects of molecules that obstruct all aspects of the hepatitis C virus (HCV) life cycle. According to Chen, 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.
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."
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 will not be able to support the reproduction and growth of the virus as much. Chen also found 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.
MEDICA.de; Source: Texas A&M University