Scientists at two
American institutions have discovered a way of
replicating the HIV-1 virus, ending a significant scientific
challenge that has slowed down research on the virus.
Since the HIV-1
virus won't replicate in monkey cells, researchers have
to use a monkey virus--known as SIVmac, or the macaque
version of simian immunodeficiency virus--to
test possible therapies and vaccines in animals.
However, vaccines and therapies that are effective on SIV
don't necessarily equal human success.
By using a
combination of genetic engineering and forced adaptation,
scientists at Rockefeller University and the Aaron Diamond
AIDS Research Center, both in New York City, have
created a version of the AIDS virus that replicates
vigorously in both monkey and human cells--a
breakthrough that researchers say has the potential to
revolutionize vaccine research.
In a paper
published in the October 6 issue of Science, Paul
Bieniasz, associate professor and head of the
Laboratory of Retrovirology, explains how he and his
colleagues maneuvered around the intrinsic immunity of
primate cells by replacing the few parts of the human
virus responsible for blocking its replication in
monkey cells with components from SIV.
the virus is a mixture of engineering and forced
evolution," Bieniasz said in the Science
article. "It sounds simple in theory, but it
took us two years to do."
Theodora Hatziioannou, the paper's first author and a
research scientist in the lab, had to overcome two key
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.
the capsid region of the HIV-1 genome for the monkey
virus and then selectively growing the viruses that
replicated most vigorously over several generations,
Hatziioannou created an HIV-1 mutant that could get
past the monkey cells' TRIM5 recognition.
Another feat of
engineering was required to get around the second
obstacle: APOBEC proteins produced by a host typically force
invading viruses to mutate to such an extreme that
they cannot survive, but HIV-1 uses a protein called
Vif to destroy APOBEC proteins, preventing any attack.
in monkeys, however, aren't susceptible to the human
virus's Vif. So Hatziioannou did another
switch--the SIV Vif gene for the HIV gene. Then
there was another round of forced adaptation to create
viruses that would multiply with vigor.
named their end result simian tropic HIV (stHIV)--a
form of HIV-1 that is only different from the original
by about 10% but still effectively infects primate
cells and can be used to test potential therapies and
Bieniasz said in
the article, "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." (The Advocate)