Wednesday, September 14, 2011

Glowing cats could help in AIDS research

In an effort to create new methods for research on AIDS, scientists have made transgenic cats that possess a green fluorescent glow. How is a glowing cat useful, you might ask. Well, the researchers made a genetic construct that links a gene that protects against HIV infection to a gene that causes green fluorescence, the famous Green Fluorescent Protein (GFP). The HIV protection gene is named TRIMCyp, and is derived from Rhesus monkeys, which are known to be HIV resistant. The whole construct is transfected into the germline of a domestic cat, which means as much as that the offspring will have the genetic construct in all of their cells. And it appears that cats possessing TRIMCyp are in fact resistant against HIV. This could be a promising lead for the development of HIV protection in humans.

The beauty of the genetic construct lies in the fact that when a newborn cat has correctly received TRIMCyp-GFP built in its cells, expression of the TRIMCyp gene is accompanied by expression of GFP, which means that cats carrying the protection gene will have a fluorescent glow: an easy way to see whether the transfection was successful. Now, with the transgenic cats, the scientists have a model which they can use to study this novel method in AIDS prevention.

But why cats? It is known that cats can be infected by a feline variant of HIV, which is called FIV. The infection and the corresponding disease are comparable with the human kind, which is why the domestic cat serves as a suitable model for research regarding HIV infection and prevention. Preliminary tests with infecting TRIMCyp cats with FIV shows that HIV is unable to replicate inside lymphocytes, immune cells that are targeted by FIV and HIV. It is however unknown if FIV is unable to infect the cat cells, or whether the virus is unable to cause the disease after infection.

Rhesus monkeys, and other species, are resistant to HIV infection because they possess a factor called Trim5α. It associates with the capsid that wraps around the harmful genetic code of HIV, preventing uncoating of the virus material into the cell, thus making replication impossible. Researchers have long sought for a way to use this protection mechanism to develop a method for HIV protection in humans. Gene therapy could prove to be the answer, however, this is still controversial for use in humans, and recent years have not yielded any real human gene therapies. Despite the fact that scientists have hallowed gene therapy as a new wonder cure for many years. The transgenic cat method to protect against AIDS does seem promising though. Of course, it will take many more years to properly investigate and unravel the protection mechanism and translate it to novel human therapeutics.

Ironically, to induce transfection in order to protect from virus infection, you need to infect animals with a virus: transfection of the TRIMCyp-GFP construct is performed by building it into a virus, and infecting the cat with it.

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