Viruses are known to be pathogens ranging from unpleasant to deadly, such as the common cold viruses (rhinoviruses), SARS-CoV-2 and HIV. However, “attenuated versions” of different viruses are useful as gene carriers for scientists to differentiate cells and alter cell functions. A “Virus Service Team” from the Austrian Institute of Science and Technology (ISTA) in Klosterneuburg (Lower Austria) is building such shuttle genes for research purposes, ISTA reported in a broadcast.
ISTA researchers use genetically modified viruses for biological research (avatar)
Genetic material can be introduced into cells for study using specially made viral gene vectors in the laboratory, which are derivatives of natural viruses. According to the bioengineers working with Flávia Leite, this will make it possible, for example, to follow step by step the mechanisms of growth, movement and metabolic activities in cells.
Natural viruses are small molecular machines that are highly efficient in infecting host cells and causing them to produce viral particles. Most are smaller than the shortest wavelength of visible light (violet at 380 nanometers = one billionth of a metre). According to Leite, they are spread all over the world.
Viruses become harmless
Viruses consist of a protein envelope that is sometimes (as in the case of the coronavirus) surrounded by an extra lipid shell. These coatings protect the viral genome, as it has been written that many new viruses can be produced from infected cells. The host cells involuntarily take on this task, usually damaging themselves as a result.
“In the virus service lab, we use modified viruses that are no longer dangerous,” says Light. “You can infect cells, that is, penetrate them, but they are not contagious and they cannot jump to a new host,” she explained to APA: Once the scientists use them in the experiment, the virus’ gene shuttles will be used. It cannot infect new cells or even another human or animal. “Your only job is to deliver proteins into cells,” says the bioengineer.
Researchers are handling virus gene shuttles in biosafety workbenches in biosafety laboratories (protection level 1-2, SARS-CoV-2 viruses should not be allowed to reproduce here) because they could theoretically infect virus genetic shuttles, Light says: This would affect the risk Only on the researchers themselves, because viruses, which have been degraded into gene vectors, cannot spread further. “They were created in a very careful way so that they don’t contain any of the genes that allow them to produce new viruses,” explains Light.
Viruses as molecular tools
And instead of the original genetic material for viral replication, it carries any gene in cells that researchers want to learn more about, she says. Part of this genetic code is designed to be inserted into the normal genome of a cell.
With so-called “gland-associated viruses” one can produce, for example, a green fluorescent protein (green fluorescent protein – GFP). The target cells, or some of the structures within them, are then seen glowing green under a microscope if irradiated with ultraviolet light. In addition to green, there are also blue, red and yellow fluorescent proteins, so it will be possible to distinguish many different structures in color in order to monitor their development.
“Our viruses also act as molecular tools. You can use them to turn a gene off, for example, in order to understand what role it plays in the cell,” says Light. Also, researchers sometimes change genes to be turned on and off by flashes of light. “Adenomyosis-related viruses are particularly useful for neuroscientists because they target different types of brain cells,” the researcher explains. This means that you can search individual brain structures.
The possibility of generating continuous cell lines
The ‘lazy viruses’, in turn, have the ‘special ability’ to make pieces of genetic material (DNA) that carry an integral part of a cell’s genome. “In this way, the introduced DNA is transferred to the offspring of the cell, and we can generate continuous cell lines,” says Light. Here, too, green fluorescent protein can be introduced. “In ISTA, for example, Sandra Siegert uses them to track microglia immune cells in the brain, and Michael Sixt uses lentiviruses to monitor immune cells moving through dense tissue.”
The ISTA Virus Service team in Klosterneuburg also produces derivatives of rabies viruses. “While it is very dangerous in its natural form, in the lab it can help neuroscientists map the connections in the brain,” says Mark Smith, virus service technician. “When used correctly, it infects neurons in the opposite direction of information flow. In the brain .” The information pathway thus becomes visible under the microscope as the virus causes neurons to produce fluorescent proteins.
(APA/red, photo: APA/APA/dpa/gms/dkfz/A9999 Dkfz)