Glimpse of How HIV Alters Cells Tom Abate
August 06, 2001
c.2001 San Francisco Chronicle
Researchers at the University of California at San Diego have
published the first detailed glimpse of how HIV progressively
hijacks the genetic machinery of infected cells, ultimately causing
them to commit suicide.
In a recent article in the journal Genome Research, a team led
by UC San Diego scientist Jacques Corbeil offered what amounts to a
time-lapse study of an infection in progress. Their study reveals
how, during the first 30 minutes after infection, HIV turns off
nearly 500 genes and switches on some 200 genes that shouldn't be
active.
``We took multiple snapshots of the genes at multiple points in
time,'' Corbeil said.
In this case the snapshots weren't taken with a camera, but with
DNA chips. These are small slices of glass containing bits of
genes. The gene fragments on the chip act like strips of smart,
genetic Velcro. Each gene fragment is designed to catch one and
only one gene.
When a sample from a diseased cell is dropped onto a DNA chip,
the fragments grab the active genes in the sample. Scientists use
special instruments to detect where these matchups occur to figure
out which genes are active.
In the UC San Diego experiment, Corbeil's team exposed a special
culture of CD4+ T cells to a huge dose of HIV. These CD4 cells help
the immune system respond to infections. Scientists have long known
that HIV attacks these defensive cells, but they have never had a
large-scale, in- depth look at the attack in progress, Corbeil
said.
The UC San Diego scientists used a DNA chip made by Affymetrix,
a biotech firm in Santa Clara. The chip they used was capable of
capturing the activity of 7,000 of the roughly 30,000 human genes.
(Chips capable of 7,000 readings were state of the art when the
experiment was done; the scientists are repeating the experiment
with new DNA chips that pack more fragments onto a single chip.)
To get the story over time, the scientists dropped samples from
the infected cells onto these DNA chips at eight intervals, from 30
minutes after infection to 72 hours later, when the cells began to
die.
They repeated these steps with samples drawn from uninfected CD4
cells. Comparing the gene activity between the infected and
uninfected samples will provide clues about how HIV wrecks the
genetic machinery.
Corbeil said one of the surprises was the type of genes HIV
changed.
``They're involved in DNA repair and other aspects of cell
maintenance,'' he said.
Tom Gingeras, vice president for biological sciences at
Affymetrix and one of the authors of the paper, said the team's
working hypothesis is that HIV subverts so much of the genetic
machinery that other control mechanisms initiate apoptosis, or cell
suicide.
``HIV has picked this cell out of all the other possible
cells,'' Gingeras said. ``If it can defeat those CD4 cells, it can
defeat the first line of defense against itself.''
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