Researchers have genetically modified domestic cats to resist the feline form of AIDS. Expression of the green fluorescent protein in this five month old transgenic cat indicates that it has acquired the protective gene.
Credit: Mayo Clinic
The transgenic kitten is photographed next to a non-transgenic control cat to illustrate the expression of the fluorescent protein.
Credit: Mayo Clinic
BRISTOL: Domestic cats have been genetically modified to resist the feline form of AIDS in a new study that could have significant implications for health researchers working to protect humans from the virus.
Cats and humans are both afflicted with pandemic AIDS lentiviruses - a type of retrovirus characterised by a long incubation period.
The feline equivalent to the human virus, HIV-1, is known as feline immunodeficiency virus (FIV). These two viruses are very similar both in their genomic structure and in the way the disease manifests within the host.
Researchers based out of the Mayo Clinic, a non-profit medical research centre in the U.S., recently introduced the genetic code for proteins known to inhibit the replication of both HIV-1 and FIV into the DNA of cats.
"For the first time we have the ability to manipulate protection genes into an AIDS susceptible animal," said Eric Poeschla, an infectious diseases virologist at the Mayo Clinic College of Medicine, and senior author on the paper published in Nature Methods.
Glowing success
The genetic modification of cats is not new. However, previous studies have used cloning techniques that are inefficient and produce abnormalities in the clones. Poeschla and colleagues used a method not previously used for carnivores that is both efficient and versatile.
Two genes were introduced into a lentivirus, which was then inserted into egg cells harvested from discarded ovaries from normal spaying procedures. The egg cells were then fertilized and implanted into a foster mum.
The two genes introduced were the TRIMCyp gene, from rhesus macaques, which codes restriction factors for FIV and HIV-1 and the eGFP gene, from jellyfish, which codes green fluorescent protein.
The green fluorescent protein was used to easily determine whether the genes had been successfully incorporated into the cat DNA. If the cats glowed under a special light, the transfer and expression was successful.
The transgenic cats have already been bred and their offspring have inherited their parent's green glow along with the FIV resistance. This means that the manipulated DNA has passed on successfully as an inherited trait and shows the potential for developing disease resistant genetic lines.
Potential for HIV and AIDS protection
White blood cells cultured from the transgenic cats showed resistance to FIV replication, but studies into how the whole animal would fare when exposed to FIV are yet to be done.
"At this point, we don't know whether the whole animal is protected from acquisition of the virus or development of the associated illness," said Poeschla. "Whole-body animal testing will have to be done."
HIV research and therapies are just starting to explore stem cell and gene therapies as alternatives to powerful drugs.
"In the future, we might engineer people's cells by adding a gene that encodes resistance, not to the whole body, but to the T-cells that are targeted by HIV" commented Paula Cannon, a geneticist at the University of Southern California's Keck School Of Medicine, who was not involved in the study but specializes in HIV-1 research and gene therapy.
"This research has given us the tools to explore whether these host cell restriction factors can be used to develop an HIV gene therapy."
Gene therapy for conservation
The transgenic cats created by Poeschla and his colleagues may also have important applications for the conservation of threatened species.
Species with very few remaining individuals due to habitat loss and depletion of resources have less genetic diversity, and are less likely to have the genetic coding to help them resist disease.
The Iberian lynx has an estimated 250 individuals remaining and is susceptible to the feline leukemia virus. In 2008, the koala retrovirus was linked to 80% of captive koala deaths in Queensland, Australia.
It's possible that in the future gene therapy may be considered for small populations of endangered species threatened by disease.
