HIV has proved to be a stubborn foe, but its relatives that infect animals could help us make a run around the virus’s defenses.
Of Mice and Men and HIV
One hurdle in HIV research is that the virus is very human-specific, so it doesn’t readily infect lab animals—and looking at cells in a Petri dish isn’t enough to develop safe and effective treatments. One approach that’s been used is to “humanize” lab mice by replacing most of their immune system with human cells that are vulnerable to the virus. The mice get infected and exhibit some symptoms of AIDS.
But humanized mice are still not ideal, according to Theodora Hatziioannou, a scientist at the Aaron Diamond AIDS Research Center. Mice are “a limited model,” she says, that “[does] not accurately mimic all interactions” between human systems and HIV.
Ideally, researchers would want to be able to observe the virus in a primate, but HIV proves to be too attuned to our own systems to thrive in our closest animal relatives (HIV can infect chimpanzees, but they do not progress to AIDS-like symptoms). To get to our primate model, we have to turn to the monkey-specializing cousin of HIV, which is thought to be the precursor of HIV.
Monkeying Around With SIV and HIV
The simian immunodeficiency virus, or SIV, has been lurking in monkeys and apes for at least 32,000 years, but in many primates, SIV does not cause disease. However, when one strain of SIV adapted to infect macaques, the result was SIVMAC, which is incredibly pathogenic and results in effects similar to AIDS. So it is possible to study SIVMAC as an HIV surrogate, but still not quite ideal. Why not? One reason, says Hatziioannou, is that the simian virus is still genetically quite distant from HIV.
The other main piece of Hatziioannou’s work is the pigtailed macaque (so named for their short, slightly curled tails). A few years ago, researchers figured out that these medium-sized monkeys lack a particular protein called TRIM5, which in other Old World monkeys confers resistance to HIV—a tantalizing prospect for an HIV model, if one could make sure that the virus could replicate and eventually cause AIDS. Hatziioannou and her team took HIV, added bits from SIVMAC that allow the engineered virus to replicate inside macaque cells, and infected some pigtailed macaques. Their results were published in June 2014 in the journal Science.
“The original virus replicated but didn’t cause disease,” Hatziioannou says. To encourage the virus to adapt, they took blood from one infected monkey and inoculated another. “By the fourth passage, we had the first animal succumb to AIDS disease.”
There’s still some refinements to be made with the macaque model; for the monkeys to progress to AIDS, the researchers have to artificially suppress their immune systems early on in infection. “Ideally we would want virus to cause AIDS in immunologically intact animals,” Hatziioannou says.
And while this HIV model might not immediately translate into benefits for wild macaques suffering from SIV, other research teams have already developed a vaccine that can protect against SIV infection.
Cat Got Your Vaccine?
Like many primates, cats have reached a kind of uneasy truce with their HIV analogue. Feline immunodeficiency virus (FIV) does cause a depressed immune system that leaves cats vulnerable to secondary infections. But FIV is not as readily transmitted as HIV; while it can be transferred from an infected cat to another by a deep bite, FIV generally isn’t transmitted via sexual contact, and it’s rare for infected mother cats to pass the virus to their kittens.
University of Florida researcher Janet Yamamoto, who first discovered FIV, has been investigating the virus to see what clues it might provide to fighting HIV—in particular, how it might aid the development of a vaccine. Yamamoto and her colleagues have been developing an HIV vaccine that can place the T-cells of the immune system—those all-important pathogen-fighting white blood cells—on guard against HIV. As they described in a 2013 paper in the journal Virology, when Yamamoto’s team took T-cells from HIV-positive human patients and exposed them to snippets of FIV, they discovered one region of the feline virus that induced the T-cells to destroy HIV when they were subsequently exposed to the human virus.
“[We need to] test these regions as vaccine components in cats against FIV, and monkeys against SIV, before phase-I clinical trials in humans,” Yamamoto told Medical News Today. In addition to illuminating the way to an HIV vaccine, “the by-product of this work will be the production of improved second-generation FIV vaccine. Thus, our work will benefit both humans and cats.”
By: Roxanne Palmer