HIV gets a Makeover -- MEDICA - World Forum for Medicine

Researchers up to now had to face a problem 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.

Paul Bieniasz, associate professor and head of the Laboratory of Retrovirology, and his colleagues succeeded in manoeuvring 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. 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. “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.”

The researchers 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 they created an HIV-1 mutant that could evade the monkey cells´ TRIM5 recognition.

The second obstacle were APOBEC proteins. These are normally produced by a host and 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´ Vif. So the researchers 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 vigour.; Source: Rockefeller University