Viruses are known to be pathogens that range from annoying to deadly, such as common cold viruses (rhinoviruses), SARS-CoV-2 and HIV. However, “slimmed-down versions” of various viruses are useful as gene carriers for scientists to mark cells and change cell functions. A “virus service team” from the Institute of Science and Technology Austria (ISTA) in Klosterneuburg (Lower Austria) is constructing such gene shuttles for research purposes, the ISTA reports in a broadcast.
<!–
ISTA researchers use genetically modified viruses for bio-research (symbol image)
Virus gene carriers, which are derivatives of natural viruses, have been specially created in the laboratory and can be used to introduce genetic material into cells in order to study them. According to the bioengineers working with Flávia Leite, this will make it possible, for example, to follow mechanisms for growth, movement and metabolic activities in cells step by step.
Natural viruses are tiny molecular machines that are highly efficient in infecting host cells and causing them to produce virus particles. Most of them are smaller than the shortest wavelength of visible light (violet at 380 nanometers = billionths of a meter). According to Leite, they are spread all over the world.
Viruses rendered harmless
Viruses consist of a protein shell, which is sometimes (as in the case of the coronavirus) surrounded by an additional fatty shell. These coatings protect the viral genome, on which it is written that many new viruses can be produced from the infected cells. This task is involuntarily taken over by the host cells, which usually damage themselves as a result.
“In the Virus Service laboratory, we use modified viruses that are no longer dangerous,” says Leite. “You can infect the cells, i.e. penetrate them, but they are not contagious and cannot jump into a new host,” she explained to the APA: As soon as the scientists use them in the experiment, the virus gene shuttles would be used up and might not infect new cells or even a human or other animal. “Your only job is to deliver proteins into the cells,” says the bioengineer.
The researchers handle the virus gene shuttles in biosafety workbenches in biosafety laboratories (protection level 1-2, no SARS-CoV-2 viruses should be allowed to multiply here) because they might theoretically be infected with the virus gene shuttles, says Leite : This risk would only affect the researchers themselves, because the viruses, which have been degraded to gene carriers, might not spread further. “They are constructed in an extremely careful way so that they don’t have any of the genes that would allow them to produce new viruses,” explains Leite.
Viruses as molecular tools
Instead of the original genetic material for virus replication, they carry any gene into the cells that the researchers want to know more regarding, she reports. Part of this genetic code is designed to be inserted into the cell’s natural genome.
With so-called “adeno-associated viruses” one can produce, for example, a green fluorescent protein (Green Fluorescent Protein – GFP). The target cells, or certain structures within them, would then be seen glowing green under the microscope if they were irradiated with ultraviolet light. In addition to green, there are also blue, red and yellow fluorescent proteins, so it would be possible to mark several different structures in color in order to observe their development.
“Our viruses also function as molecular tools,” says Leite: “You can use them to switch off a gene, for example, in order to understand what role it plays in the cell.” Also, researchers would sometimes alter genes to be turned on and off by flashes of light. ‘The adeno-associated viruses are particularly useful for neuroscientists because they target different types of brain cells,’ explains the researcher. This means that you can research individual brain structures.
Generation of continuous cell lines possible
“Lentiviruses” in turn have the “special ability” to make the pieces of genetic material (DNA) they carry an integral part of the genome of a cell. “In this way, the introduced DNA is then passed on to the cell’s offspring, and we can generate continuous cell lines,” says Leite. Here, too, the introduction of green fluorescent protein is possible. “At ISTA, for example, Sandra Siegert uses them to track microglial immune cells in the brain, and Michael Sixt uses lentiviruses to observe immune cells moving through dense tissue.”
The Virus Service team at ISTA 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 connections in the brain,” says Virus Service technician Mark Smyth. “When used properly, it infects nerve cells in the opposite direction to the flow of information in the brain.” The information path thus becomes visible under the microscope as the virus causes the neurons to produce fluorescent proteins.
(APA/red, photo: APA/APA/dpa/gms/dkfz/A9999 Dkfz)
