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e! Science News
Body's anti-HIV drug explained
Published: Sunday, October 12, 2008 - 13:28 in Biology & Nature
Learn more about: heart development hepatitis b virus hiv drugs university of
southern california viral dna virulence factor
Humans have a built-in weapon against HIV, but until recently no one knew how
to unlock its potential. A study published online by the journal Nature reveals
the atomic structure of this weapon – an enzyme known as APOBEC-3G – and
suggests new directions for drug development.
APOBEC-3G is present in every human cell. It is capable of stopping HIV at the
first step of replication, when the retrovirus transcribes its RNA into viral
DNA.
The study's authors, led by Xiaojiang Chen of the University of Southern
California, were able to show the atomic structure of the active portion of
APOBEC-3G.
The discovery suggests how and where the enzyme binds to the viral DNA,
mutating and destroying it.
"We understand how this enzyme can interact with DNA," said Chen, a professor
of molecular and computational biology at USC. "This understanding provides a
platform for designing anti-HIV drugs."
If APOBEC-3G works so well, why do people get AIDS? Because the HIV virus has
evolved to encode the protein Vif, known as a "virulence factor," that blocks
APOBEC-3G.
With APOBEC-3G out of the way, the RNA of the HIV virus can be successfully
transcribed to viral DNA, an essential step for infection and for producing
many more HIV viruses.
Chen said his group's research offers important clues on where Vif binds to
APOBEC-3G. The knowledge could be used to design drugs that would prevent Vif
from binding and allow APOBEC-3G to do its job, Chen said.
That would unlock humans' innate ability to fight HIV.
"We were born with it, and it's there waiting," Chen said.
In addition to fighting HIV, APOBEC-3G can inhibit the Hepatitis B virus. Other
members of the APOBEC family serve important roles in antibody maturation, fat
metabolism and heart development.
Mapping the structure of APOBEC-3G at the atomic level is a goal that "has been
sought after worldwide because of its significance," Chen said.
Source: University of Southern California
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