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A simple feedback resistor switch keeps latent HIV from awakening

Upon entering a cell, a virus often becomes dormant, turning off its genes and laying low until awakened by som e trigger from its environment. When that trigger is pulled, the virus quickly ramps up production of proteins through built-in positive-feedback loops that turn up gene transcription. (In positive feedback, production of something stimulates more production of that thing, resulting in exponential, or faster, growth.) If the viral environment were perfectly regulated and viral gene expression perfectly silenced during latency, this system would be foolproof. But this is almost never the case--there is always noise and always the potential for some low level of erroneous transcription. This poses a problem for the virus--how does it prevent stray transcription from erupting into full-blown activation?

Certain bacterial viruses manage this problem by encoding intricate repressor circuits that efficiently block transcription. But animal viruses, specifically HIV, appear to lack similar repressor circuits. In a new study, published online in the open access journal PLoS Biology, Leor Weinberger and Thomas Shenk propose that some animal viruses, including HIV, regulate their potential for positive feedback and maintain latency by successively modifying and dissipating, or introducing a resistor into, the main activator of transcription.

HIV's transcriptional activator, the Tat gene, is encoded in the HIV genome. Once Tat is transcribed, it can rapidly increase transcription not only of itself, but also of other genes that ultimately lead to viral replication. Thus, the Tat protein acts like a molecular switch, making it a likely target for regulating latency. In some kinds of molecular switches, the conversion between on and off states is regulated by self-oligomerization, or binding to several other identical molecules. The shape changes induced by binding or unbinding drive the complex into two different stable conformations. But , the
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Contact: Natalie Bouaravong
press@plos.org
415-568-3445
Public Library of Science
25-Dec-2006


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