Viruses of Cats and Humans

By Jason Socrates Bardi

"But the Kitten, how she starts,
Crouches, stretches, paws, and darts!
First at one, and then its fellow,
Just as light and just as yellow.
There are many now—now one—
Now they stop and there are none."

The Kitten and the Falling Leaves by William Wordsworth, 1804.

The patient's symptoms and prognosis tell an all-too-familiar tale. The patient became infected several years before and suffered an acute illness before his immune system brought the virus under control. Then he was fine and lived without symptoms for several years, but during this time the virus was quietly weakening his immune system.

Now he is not eating, losing weight, reeling from high fever, terrible diarrhea, swollen lymph nodes, and suffering from chronic opportunistic infections. The patient is in the final throes of the terrible disease that has ravaged millions worldwide—acquired immune deficiency syndrome (AIDS).

And though the story may sound familiar, the patient may not be. The patient in this imaginary case is a cat, suffering from the feline form of AIDS. Like the human disease, which is caused by the "lentivirus" human immunodeficiency virus (HIV), feline AIDS is caused by a lentivirus known as feline immunodeficiency virus (FIV).

That two such different species as humans and cats could suffer such similar diseases is perhaps not so surprising considering the similarity between the two viruses that cause these diseases. And FIV and HIV are very similar.

If you were to take an electron micrograph of human cells infected with HIV and cat cells infected with FIV and hold these two images right next to each other, you would see in both images small spiky virions with a visible pill-shaped capsid inside. They are the same size.

"It is impossible to tell them apart," says Professor John Elder, who has studied FIV since the mid-1980s at The Scripps Research Institute (TSRI), where he is currently supported by the hard work of Staff Scientist Aymeric deParseval and Research Associates Ying-Chuan Lin, Udayan Chatterji, and Sohela de Rozieres.

A Virus is Discovered and Isolated

It was in 1986, just a few years after the initial alarms had been raised about HIV, that FIV was discovered in California. In 1986, Niels Pedersen, who is currently director of the Center for Companion Animal Health at the University of California, Davis, and Janet Yamamoto, who is now a professor in the University of Florida's College of Veterinary Medicine, co-discovered FIV.

As the story goes, there was a kindly woman who took in strays—many strays—housing them in her large kennels. She noticed an odd thing. Several cats under her care became sick and eventually died seemingly as a result of sleeping in the same pen as one particular feral cat. So she contacted Pedersen, who took samples and eventually isolated a virion, which under the electron microscope looked like an RNA virus belonging to the lentivirus family.

Shortly thereafter, Elder began to collaborate with the Pedersen laboratory to work on the virus taken from that isolate and from another isolate from a cat belonging to former TSRI investigators Fred Hefron and Maggie So.

"They had a cat that came down with FIV, and we isolated the virus from it," says Elder.

Elder had been working at TSRI since the mid-1970s, and he was considered an expert in retroviruses like the newly discovered FIV. In fact, Elder and his laboratory had been working on retroviruses for 10 years by the time FIV was discovered in 1986.

"It was a natural progression for us to take our molecular tricks over there and try to find out what the structure of that virus was," says Elder.

The tricks Elder and his laboratory employed were basically those of molecular cloning—they were experts at isolating and amplifying the DNA of the virus so that it and its proteins could be studied. Basically, what this entailed was to extract the DNA from infected blood lymphocytes, chop it up with enzymes, insert the DNA pieces into phage (a virus that infects bacteria), and then infect bacteria with the phage.

Bacteria can easily be grown, providing a convenient way of amplifying the DNA. Elder and his laboratory then had only to look for the right pieces of DNA by labeling them with radioactive probes and separating them.

"We found one [piece] that contained what looked to be the whole virus," says Elder.

Then they took that piece of DNA and used it to transfect cells. They then observed those cells and found that they were productively replicating the virus, which they then isolated so that they could sequence it. Elder and his colleagues also made expression systems with many of the viral proteins so that they could be produced and purified for biochemical studies and other research.

Two Very Similar Viruses

Building on this initial work, Elder and his colleagues at TSRI and elsewhere have been able to characterize the genomic organization of FIV and, significantly, to compare it to that of its cousin HIV. FIV and HIV, it turned out, have a lot in common, which makes FIV a good model for studying an HIV-type infection.

The similarities between the two viruses go deeper than morphology. FIV, as a disease, represents as serious an epidemic for the wild and domestic cat populations in the world as HIV does for the human populations of the world.

Both are members of the lenti (slow) virus family and they contain many of the same characteristic genes and proteins. FIV, much like its human cousin HIV, has an RNA genome of around 10,000 bases that is packaged in a protein and lipid capsid and coat. HIV and FIV both code for a number of structural genes, which encapsulate the RNA and are produced by a gene called gag. In an infected cell, the virus produces a large Gag polyprotein that is later chopped up into its constituent pieces by an important viral enzyme called the protease.

The protease and a few other necessary enzymes are encoded by a viral pol gene. And HIV and FIV also encode env genes, which makes a glycoprotein that sticks up out of the coat of the virion and helps the virus infect cells.

At the amino acid level, Elder estimates, about 40 to 45 percent of the residues in FIV proteins are identical to those in HIV. "We found," says Elder, "[that the FIV and HIV sequences] were quite related."

In fact, he adds, some of the proteins are so similar that they have almost identical structures. Elder and his colleagues hope that their discoveries and successes in their research on FIV will shed light on the problem of HIV.

"One very big parallel [between the two]," says Eder, "is that FIV uses the chemokine receptor CXCR4, like many strains of HIV."

Much like HIV, FIV requires the interaction of its surface glycoprotein molecules with CXCR4. And, also like HIV, FIV requires another receptor to maximize binding to the chemokine receptor. In HIV, the required receptor is called CD4. The exact receptor needed by FIV is, at the moment, not known.

"We're trying to figure out what it is," says Elder.


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Professor John Elder is an expert on retroviruses, such as those that cause human and feline AIDS. Photo by Jason S. Bardi.