[procaare] HIV Gets Makeover: Tweaking AIDS Virus Could Alter Course Of Research

["Rockerfeller Release" <procaare@healthnet.org>]

HIV Gets Makeover: Tweaking AIDS Virus Could Alter Course Of Research
Rockefeller University :October 16, 2006
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The slow pace of AIDS research can be pinned, in no small part, on something 
akin to the square-peg-round-hole conundrum. The HIV-1 virus won't replicate 
in monkey cells, so researchers use a monkey virus - known as SIVmac, or the 
macaque version of simian immunodeficiency virus - to test potential 
therapies and vaccines in animals. But therapies and vaccines that are 
effective on SIV don't necessarily translate into human success.

Now, using a combination of genetic engineering and forced adaptation, 
researchers at Rockefeller and the Aaron Diamond AIDS Research Center have 
created a version of the AIDS virus that replicates vigorously in both human 
and monkey cells - an advance that has the potential to revolutionize 
vaccine research.

In a paper published in today's issue of Science, Paul Bieniasz, associate 
professor and head of the Laboratory of Retrovirology, describes how he and 
his colleagues maneuvered around the intrinsic immunity of primate cells by 
replacing just a few parts of the human virus - the ones responsible for 
blocking replication in monkey cells - with components from SIV. "Overall, 
the virus is a mixture of engineering and forced evolution," Bieniasz says. 
"It sounds simple, in theory, but it took us two years to do."

Bieniasz and Theodora Hatziioannou, a research scientist in the lab and the 
paper's first author, had to overcome two major obstacles: the first was a 
protein called TRIM5 that, in monkeys, recognizes the outer shell or 
 "capsid" of HIV-1 but not that of SIV. By swapping out the capsid region of 
the HIV-1 genome for that of the monkey virus, and then selectively growing 
the viruses that replicated most robustly, over several generations 
Hatziioannou created an HIV-1 mutant that could evade the monkey cells' 
TRIM5 recognition.

Another bit of engineering was required to get around the second obstacle: 
APOBEC proteins produced by a host normally cause invading viruses to mutate 
so much that they can't survive, but HIV-1 uses a protein called Vif to 
destroy APOBEC and prevent the attack. Monkey APOBEC proteins, however, aren't 
susceptible to the human virus's Vif. So Hatziioannou did another swap - the 
SIV Vif gene for the HIV one - and then another round of forced adaptation 
to create viruses that would multiply with vigor.

The researchers dubbed their end result simian tropic HIV (stHIV): a form of 
HIV-1 that only differs from the original by about 10 percent, but can 
effectively infect primate cells and be used to test potential therapies. 
"If we can make this virus work in animals the way it works in tissue 
culture, it will likely change the way that AIDS vaccine and therapeutics 
research is done," Bieniasz says.

Online: Science Daily
http://www.sciencedaily.com/releases/2006/10/061012185811.htm