麻豆传媒

AN HIV virus modified to infect monkeys could be a big step forward for HIV research.

The disclosure last month that an experimental vaccine against HIV may not be as effective as first thought highlighted a nagging problem with HIV-vaccine research: that there is no effective way of testing them in animals.

All that could change if the new animal model of HIV is successful. Current primate models use simian immunodeficiency virus (SIV), which is similar but not identical to HIV.

The new model, developed by a team led by virologist at the Aaron Diamond AIDS Research Center (ADARC) in New York, could guide future vaccine trials, drug development and basic research into the virus. 鈥淭he potential applications are huge,鈥� Hatziioannou says. 鈥淚t could change the way we do our animal research for HIV and AIDS.鈥� She presented her team鈥檚 results at in Boston last month.

Few researchers question the need for better animal models of the HIV virus, which about 33 million people are living with worldwide. In the early days of the AIDS epidemic, HIV therapies were tested on chimpanzees, the virus鈥檚 original host. But HIV doesn鈥檛 cause disease in chimps and their endangered status limited researchers鈥� use of them. So they turned to monkeys and SIVs.

Today, labs use two main varieties of SIV: one from sooty mangabeys that causes an AIDS-like disease in macaques, and a hybrid virus called SHIV, which contains a cocktail of HIV genes spliced into SIV (see 鈥淭he right virus for the job鈥�). 鈥淣either of the models corresponds to what happens with HIV in humans perfectly,鈥� Hatziioannou says. SIV thwarts the monkey immune system in a slightly different way to HIV, and SHIVs use only bits of HIV.

Hatziioannou鈥檚 new virus, developed with , also at ADARC, and researchers at the US National Cancer Institute in Frederick, Maryland, is based on two decades of research into how HIV and SIV foil immune systems. The research showed that the viruses work by overcoming two key defence proteins: TRIM5-alpha, which prevents retroviruses such as HIV from shedding their coat once they invade a cell, and APOBEC3G, which stashes itself inside newly formed viruses and sabotages their efforts to reproduce. HIV has learned to counter both of these proteins in humans, and SIVs do the same in monkeys. Yet monkey defences are not fooled by HIV.

Hatziioannou鈥檚 breakthrough was to splice into HIV the SIV gene called vif, whose protein is unaffected by monkey APOBEC3G (). The team found that the resultant virus, known as stHIV, causes a disease in pig-tailed macaques (which lack functional TRIM5-alpha) that mimics the early stages of HIV infection. This could make it a more useful tool for testing HIV drugs and vaccines than SIV or SHIV. The team also found that giving monkeys a high dose of antiretroviral drugs before infection with stHIV 鈥� a therapy being considered for people at high risk of HIV 鈥� prevented them from contracting the virus.

鈥淭he spliced virus causes a disease in pig-tailed macaques that mimics early-stage HIV infection鈥�

Hatziioannou鈥檚 team cannot rest on these accomplishments, however. Even without drugs, the monkey鈥檚 immune system eventually controls the virus and they never develop AIDS.

at the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, whose team developed a similar HIV model, says more changes will be necessary. 鈥淭here are a lot of other genes to think about if you really want to come up with a good animal model,鈥� he says.