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Amitabh Avasthi
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Increasing the production of naturally occurring proteins that
contain selenium in human blood cells slows down multiplication of the
AIDS virus, according to biochemists. "We have found that increasing
the expression of proteins that contain selenium negatively affects the
replication of HIV," said K. Sandeep Prabhu, Penn State assistant
professor of immunology and molecular toxicology. "Our results suggest
a reduction in viral replication by at least 10-fold."
Selenium is a micronutrient that the body needs to maintain normal
metabolism. Unlike other nutrients, which bind to certain proteins and
modulate the protein's activity, selenium gets incorporated into
proteins in the form of an amino acid called selenocysteine.
These proteins – selenoproteins – are especially important in
reducing the stress caused by an infection, thereby slowing its spread.
Upon infecting a person, the virus quickly degrades selenoproteins
so that it can replicate efficiently. It is unclear just how the virus
is able to silence these proteins but Prabhu and his colleagues believe
that stress inflicted on cells by the rapidly dividing virus, which
produces a key protein known as Tat, is the likely culprit.
Tat is one of about 14 odd proteins produced by HIV during the first
stage of infection. The job of these proteins is to trigger the
expression of all the other genes that the virus needs to sustain
itself. In addition, Tat also plays a key role in helping the virus
replicate.
One of the proteins that targets Tat is a selenoprotein known as TR1.
"Since HIV targets the selenoproteins, we thought that the logical
way to deal with the virus is to increase the expression of such
proteins in the body," explained Prabhu, whose team's findings are
outlined this week (Nov. 28) in the Journal of Biological Chemistry.
Researchers first isolated blood cells from healthy human volunteers
who did not have HIV, and infected those cells with the virus. Next,
they added tiny amounts of a selenium compound – sodium selenite – into
the cell culture to see the effect on viral replication.
Results from the tests indicate that the addition of selenium
inhibits the replication of HIV at least 10-fold, compared to cell
cultures in which no selenium is added. When the researchers
selectively reduced production of the selenium containing TR1 protein,
they observed a 3.5-fold increase in viral replication.
"This confirms that while increasing the expression of TR1 has a
negative impact on the replication of HIV, reducing it helps the virus
replicate more efficiently," explained Prabhu. He believes that TR1
works by upsetting the chemical structure of Tat, which in turn reduces
the virus' ability to replicate.
"Once we fully understand the function of these selenium proteins,
it will give us a handle to come up with more effective drugs," said
Prabhu, whose work is partly funded by the National Institutes of
Health.
Source: Penn State
Original article:
Parisa Kalantari,
Vivek Narayan,
Sathish K. Natarajan,
Kambadur Muralidhar,
Ujjawal H. Gandhi,
Hema Vunta,
Andrew J. Henderson, and
K. Sandeep Prabhu. Thioredoxin Reductase-1 Negatively Regulates HIV-1 Transactivating
Protein Tat-dependent Transcription in Human Macrophages. J. Biol.
Chem., Vol. 283(48), 33183-33190, November 28, 2008.
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