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U.S. researchers said Thursday they have finally infected a species of monkey called pigtailed macaques with an AIDS-like disease after years of trying, a major step toward an animal model with which to study HIV-1, the virus responsible for most cases of AIDS.
HIV-1, a very selective virus, does not readily infect species other than its usual hosts -- humans and chimpanzees, which has made the search for effective treatments and vaccines for AIDS much more difficult, researchers at the Rockefeller University and the Aaron Diamond AIDS Research Center said.
The reason is simple as without an accurate animal model of the disease, researchers have had few options for clinical studies of the virus.
"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," Paul Bieniasz of the Rockefeller University said. "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."
According to the researchers, although pigtailed macaques have fewer defenses against HIV-1 than most other primates, they lack an antiviral protein that fights off the virus. As a result, the researchers altered both the virus and the macaque immune system 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, and then 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," said Theodora Hatziioannou of Aaron Diamond. " 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."
HIV therapy and prevention research often relies on SIV 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," Hatziioannou added.
The findings were published in the U.S. journal Science.
