Transgenic cats shed (green) light on HIV immunity - but is it any use?

Transgenic - GFP cats

There are currently two AIDS pandemics raging across the world: the well-known one in humans and the less recognised one in domestic cats. Feline AIDS, caused by the feline immunodeficiency virus (FIV) - a close relative to HIV - is pretty similar to that afflicting millions of humans and could potentially be used as a model system for studying HIV infection and disease. One major scientific barrier to HIV research in primates is the difficulty in generating transgenic animals efficiently. This, however, could be sidestepped through employing FIV/domestic cat as the experimental system.

The 9,000 year-long relationship between the human species and domestic cats has brought a lot to each respective species: we get rid of nasty pests and enjoy the whole 'cat experience' while they feast on the human-associated rodents and gain some shelter and people love. But what some people might not realise is that the domestic cat has - and will probably continue - to help us in biomedical research. And, for them, the increased research into cat biology may also spill over into non-domestic species, who are on the brink of extinction and might be aided by this work.

A paper published this week in Nature Methods (see paper here), documents the first reported efficient generation of transgenic domestic cats. Other cats had been produced before but not as easily as with this protocol. These animals were engineered to express an anti-SIV molecule or GFP through a lentivirus-based method. The highlight the influence of host restriction factors - in this case the TRIM proteins - on AIDS-virus infections. These TRIM proteins are cytoplasmic sensors of retroviruses that can inhibit infection and promote immune signalling in cells attacked by retroviruses.

Transgenic - TRIM expressing cat cells are resistant (black triangles) to FIV when compared to controls (grey circles)

The group - based at the Mayo Clinic College of Medicine in Minnesota, USA - generated retroviruses that contained different genes within their genome to infect cat oocytes followed by in vitro fertilization with cat sperm. The resulting embryos uniformly expressed the genes which were in this case different fluorescent proteins - like GFP - or primate antiviral molecules and were implanted into other cats. The transgenic kittens were then mated with each other to test whether they retained full fertility - which they did. And finally, when antiviral-transgenic cat lymphocytes were challenged with FIV the infection was dramatically halted.

Seeing the genotypic numbers of inserted retroviral genomes and the expressed GFP in newly born kittens

But what will this research do for biomedical research, in general?


The ease at which this was achieved may speed up some potential studies using cats. The one major problem is that the gene was expressed in every tissue - and I'm not sure that we know enough about cat biology to target this more specifically to particular tissues. But, for many diseases I am sure this model system will not be applicable and where the usual brigade of mice and rats will be more than sufficient. Yet the use of transgenic cats will, nonetheless, add to the number of potential models out there and may specifically be great for HIV/AIDS research.

As the group outlines:

Introducing a lentiviral restriction factor(s) into the genome of the cat has specific potential because this species is naturally susceptible to lentiviral infection (and AIDS) whereas mice, unmodified or transgenic, are not. Several questions can therefore now be addressed. First, it is unknown whether introducing a single active restriction factor into the genome of an AIDS virus–susceptible species can protect it, and if so, at which of three broadly considered levels: transmission, establishment of sustained viremia and disease development. When antiviral genes are interrogated at the whole animal level by transgenesis in a natural host, results can be surprising and informative.

Wongsrikeao, P., Saenz, D., Rinkoski, T., Otoi, T., & Poeschla, E. (2011). Antiviral restriction factor transgenesis in the domestic cat Nature Methods DOI: 10.1038/nmeth.1703