By altering just one gene in HIV-1, scientists have succeeded in infecting pig-tailed macaque monkeys with a human version of the virus that has until now been impossible to study directly in animals.
The new strain of HIV has already been used to demonstrate one method for preventing infection and, with a little tweaking, could be a valuable model for vetting vaccine candidates.
A team of researchers led by Paul Bieniasz and Theodora Hatziioannou at The Rockefeller University showed that two pig-tailed macaques, given a common antiretroviral treatment one week before and one week after being exposed to the newly engineered HIV, had no signs of infection. "We're not saying we can save the world with antiretroviral pills. But this model will allow us to start studying the best way to administer prophylaxis and do other experiments on preventing HIV-1 infection that could not be easily done on humans," says Bieniasz, head of the Laboratory of Retrovirology at Rockefeller and associate professor at the Aaron Diamond AIDS Research Center.
The findings, to be published Monday in the Proceedings of the National Academy of Sciences , show that the engineered virus injected into a pig-tailed macaque initially spreads almost as ferociously as it does in people and that the virus remains detectable for at least six months. But it does not make the monkeys sick. Rather, it behaves as it is thought to behave in a group of HIV-positive people whose exceptional immune systems are generally able to keep the virus in check. These fortunate few are called long-term nonprogressors.
The animal model grew out of years of research into the molecular cloak-and-dagger fight between HIV and the cells of the host it infects. In particular, Bieniasz, who is also a Howard Hughes Medical Institute investigator, Hatziioannou and colleagues have studied two groups of rapidly evolving genes, APOBEC3 and TRIM5 , that produce unusual classes of defensive proteins with distinctive capabilities to fight retroviruses such as HIV. These genes, shared by humans and their simian forebears, have evolved mutations specific to each species's unique history of retroviral battles. In most simians, the APOBEC3 and TRIM5 proteins actually kill HIV on sight, making it impossible for researchers to study the virus in an animal model. Instead, they have studied HIV's cousin, simian immunodeficiency virus (SIV), which causes an AIDS-like disease in certain monkey species. But SIV shares only about half of its amino acid sequence with HIV, making it a very imperfect substitute for testing anti-HIV drugs and vaccines. Several labs have engineered hybrids called SHIVs - SIVs that contain pieces of HIV DNA - but these have problematic differences, too.