Genetic circuit in HIV shows promise for therapyMarch 17th, 2008 - 6:00 pm ICT by admin
London , Mar 17 (ANI): Scientists from the University of California , San Diego and Oak Ridge National Laboratory, have discovered the mechanism by which a genetic circuit in HIV controls whether the virus stays dormant or turns on.
This new insight has led the scientists to successfully turning the virus dormant, showing promise for HIV therapy and understanding of cellular decisions.
The study was led by Leor S. Weinberger, professor of chemistry and biochemistry at UC San Diego, with Michael L. Simpson of Oak Ridge National Laboratory and Roy D. Dar of the University of Tennessee, Knoxville, who claimed to show how a developmental decision between HIVs two replication fates is made.
The researchers measured the level of noise or randomness in HIV gene expression and used this noise to explore how HIV makes a decision to replicate or remain dormant.
This mechanism is similar to locating a radio station by tuning in on regions with the most static.
Thus it gives a new tool for searching cellular, as well as viral, regulation, and for providing knowledge on how other biological decisions are made, particularly how stem cells choose between different developmental fates.
Its significant for two reasons. First, many researchers are interested in determining which cellular processes generate biological noise. We, instead, asked if the cellular noise could tell us anything about HIV and the cell and it did, Nature quoted Weinberger, as saying.
What it told us is how a developmental decision is made by HIV. We still dont understand how developmental decisions are made at the single-cell level — for example, how a particular stem cell differentiates into many different cell types — and whether noise can drive this decision. Surprisingly, viruses appear to be good models for understanding this type of cellular decision-making, he said.
For the study, the researchers examined the genetic master circuit of HIV, the Tat circuit, and relied on findings of previous work by Weinberger that showed that it did not function like a standard on-off switch.
The earlier work discovered that the HIV circuit is managed by cellular noise, or random events, activating the circuit for a limited amount of time before it turns off.
In this study, the researchers successfully exploited this noise in the HIV Tat circuit fro calculating the time for which HIV remained activated in the cell, and inferred that the time spent in the active state propelled HIVs decision to destroy the cell or not.
Later the researchers elevated the levels of the native cellular gene SirT1 (a gene implicated in aging) for reducing the lifespan of the HIV virus and force HIV-infected cells to go dormant.
Studies are being carried out so that this approach can be used for anti-HIV therapy.
The findings of this study are published in the latest issue of the journal Nature Genetics. (ANI)
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