New monkey model for AIDS offers promise for medical research

June 19, 2014, Rockefeller University

HIV-1, the virus responsible for most cases of AIDS, is a very selective virus. It does not readily infect species other than its usual hosts – humans and chimpanzees. While this would qualify as good news for most mammals, for humans this fact has made the search for effective treatments and vaccines for AIDS that much more difficult; without an accurate animal model of the disease, researchers have had few options for clinical studies of the virus.

New work from Paul Bieniasz's Laboratory of Retrovirology at The Rockefeller University and the Aaron Diamond AIDS Research Center and Theodora Hatziioannou's Laboratory, also at Aaron Diamond, may help fill this gap. In research described today in Science, they announce that they have coaxed a slightly modified form of the HIV-1 to not only infect pigtailed , a species of monkey, but to cause full blown AIDS in the primates, a first.

"HIV-1 only causes AIDS in humans and chimpanzees, but the latter are not a practical model and are no longer used for HIV/AIDS research. Our goal has been to figure out how HIV-1 could cause disease in a new host," Bieniasz says. "By accomplishing this with macaques, we have taken a step toward establishing a new model for AIDS that can be used universally in prevention and treatment research."

Although pigtailed macaques have fewer defenses against HIV-1 than most other primates—they lack an antiviral protein that fights off the virus—the researchers still had to alter both the virus and the macaque in order to induce AIDS.

They bolstered the virus with a defense-disabling protein made by Simian Immunodeficiency Virus (SIV), a relative of HIV-1. Then they encouraged the modified HIV strain to adapt to its new host by passing it from one monkey to another, resulting in six generations of infected monkeys and an adapted virus. Even so, the monkeys' immune systems were still able to control the HIV-1 infection. So, the researchers temporarily weakened their immune systems by depleting a type of white blood cell, known as a CD8 T-cell, that destroys virus-infected cells.

"When we depleted their CD8 cells, the infected monkeys developed disease closely mirroring that of human patients. For example they contracted AIDS-defining conditions including pneumocystis pneumonia, a textbook example of an opportunistic infection in AIDS," says Hatziioannou. "Because it replicates what happens when HIV-1 compromises a human patient's immune system, our approach could potentially be used in the development of therapies and preventative measures for human patients."

In fact, if fully developed, the macaque model will offer a substantial improvement for research. Often, HIV therapy and prevention research relies on SIV, a viral relative of HIV-1, since SIV can cause AIDS-like disease in nonhuman primates. However, SIV doesn't always behave the same way HIV-1 does. "We still have one major hurdle to overcome: If we could get HIV-1 to cause AIDS without depleting the CD8 cells, we could replace models that make use of SIV for this research."

This work and previous research in the lab has also illuminated the process by which HIV-1 and other members of the lentivirus family can colonize a new host like the macaques. It turns out that evading or fighting off the antiviral proteins produced by the new host's cells is key.

"This for HIV-1 infection is the result of years spent exploring scientific questions about how the virus interacts with a host's antiviral defenses. These kinds of basic insights will enable us to continue to improve this model," Hatziioannou says.

Explore further: Can marijuana protect the immune system against HIV and slow disease progression?

More information: "HIV-1–induced AIDS in monkeys," by T. Hatziioannou et al. … 1126/science.1250761

Related Stories

Can marijuana protect the immune system against HIV and slow disease progression?

February 18, 2014
New evidence that chronic intake of THC, the primary psychoactive ingredient in marijuana, can protect critical immune tissue in the gut from the damaging effects of HIV infection is reported in AIDS Research and Human Retroviruses.

AIDS vaccine candidate appears to completely clear virus from the body

September 11, 2013
An HIV/AIDS vaccine candidate developed by researchers at Oregon Health & Science University appears to have the ability to completely clear an AIDS-causing virus from the body. The promising vaccine candidate is being developed ...

Breakthrough in HIV/AIDS research gives hope for improved drug therapy

May 16, 2014
The first direct proof of a long-suspected cause of multiple HIV-related health complications was recently obtained by a team led by the University of Pittsburgh Center for Vaccine Research (CVR). The finding supports complementary ...

Platelets block HIV

July 23, 2013
Scientists of the DPZ have shown that platelet activation inhibits the host cell entry of HIV

Recommended for you

Researchers find new way to defeat HIV latency

March 8, 2018
HIV, the virus that causes AIDS, has a secret life. Though anti-retroviral therapy can reduce its numbers, the virus can hide and avoid both treatments and the body's immune response.

Broadly neutralizing antibody treatment may target viral reservoir in monkeys

March 5, 2018
After receiving a course of antiretroviral therapy for their HIV-like infection, approximately half of a group of monkeys infused with a broadly neutralizing antibody to HIV combined with an immune stimulatory compound suppressed ...

HIV begins to yield secrets of how it hides in cells

March 2, 2018
UC San Francisco scientists have uncovered new mechanisms by which HIV hides in infected cells, resting in a latent state that evades the body's immune system and prevents antiviral drugs from flushing it out.

HIV exports viral protein in cellular packages

February 15, 2018
HIV may be able to affect cells it can't directly infect by packaging a key protein within the host's cellular mail and sending it out into the body, according to a new study out of a University of North Carolina Lineberger ...

Can gene therapy be harnessed to fight the AIDS virus?

February 13, 2018
For more than a decade, the strongest AIDS drugs could not fully control Matt Chappell's HIV infection. Now his body controls it by itself, and researchers are trying to perfect the gene editing that made this possible.

Big data methods applied to the fitness landscape of the HIV envelope protein

February 7, 2018
Despite significant advances in medicine, there is still no effective vaccine for the human immunodeficiency virus (HIV), although recent hope has emerged through the discovery of antibodies capable of neutralizing diverse ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.