Genetic 'on-off' switch for anti-HIV therapy
A genetic circuit in HIV that decides whether it switches on or stays dormant could hold the key to anti-HIV therapy, according to a new study.
As part of the study, researchers at the University of California have in fact been able to "switch off" the circuit, driving HIV to dormancy.
The study has also provided a new tool for probing cellular and viral regulation, and for understanding how stem cells choose between different developmental fates.
Findings of the study have been published in the latest issue of the Journal Nature Genetics.
Leor S Weinberger and his colleagues said their study was able to measure the level of "noise", or randomness, in HIV gene expression and use it to probe how HIV decides to replicate or remain dormant.
"It's significant for two reasons," said Weinberger. "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. What it told us is how HIV makes a developmental decision," Weinberger said.
It is however still not clear 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.
The authors explored the genetic master circuit of HIV, the Tat circuit, and built upon previous work by Weinberger, which showed that it did not function like a standard on-off switch (a light switch, for example).
Weinberger's previous work found that the HIV circuit is driven by cellular noise, or random events, which activate the circuit for limited time before it turns off.
Weinberger was able to exploit this noise in the HIV Tat circuit to measure how long HIV remained activated in the cell, and deduce that the time spent in the active state drove HIV's decision to destroy the cell or not.