Scientists have developed a new animal model for AIDS research by modifying how the HIV-1 virus interacts with the immune system of the pigtail macaque monkey.
After decades of research, a reliable animal model has thus far eluded science given that HIV-1 only causes AIDS in humans and chimpanzees –– the latter deemed impractical for study and no longer used in laboratories. To induce AIDS in the monkey, collaborators from The Rockefeller University and the Aaron Diamond AIDS Research Center strengthened the virus with an aggressive defense-busting protein taken from the Simian Immunodeficiency Virus, a cousin to HIV-1. After allowing the virus to adapt among infected monkeys, the researchers temporarily weakened the animals’ immune system by targeting CD8-T cells that normally destroy cells infected with the HIV-1 virus.
Paul Bieniasz, who leads the university’s Laboratory of Retrovirology, says the new animal model will change the course of AIDS research.
"Our goal has been to figure out how HIV-1 could cause disease in a new host," Bieniasz said in a press statement. "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."
Researcher Theodora Hatziioannou, who co-authored a paper published Thursday in Science, says the new animal model closely mirrors the human experience with the virus.
"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,” she said in the statement. "When we depleted their CD8 cells, the infected monkeys developed disease closely mirroring that of human patients.”
Those disease symptoms included the “textbook example” of pneumocystis pneumonia, the Hatziioannou said. Still, the new animal model is not an exact replica of the human immunological response, she added, given the need to first deplete immune cells. "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,” she said.
However, the research successfully demonstrates that beating the immune system’s antiviral proteins is integral to infecting laboratory monkeys with HIV-1 and other lentiviruses. "This new model for HIV-1 infection is the result of years spent exploring scientific questions about how the virus interacts with a host's antiviral defenses,” Hatziioannou said. “These kinds of basic insights will enable us to continue to improve this model.”
Source: Bieniasz, Paul, Hatziioannou, Theodora, et al. New monkey model for AIDS offers promise for medical research. Science. 2014.