center for systems

& synthetic biology

an NIGMS national systems biology center


A Hardwired HIV Latency Program

February 26, 2015

In dual papers in the current issue of Cell, researchers in the lab of Center Investigator Leor Weinberger demonstrate that the establishment of HIV latency operates autonomously from cell state transitions in infected cells. 


HIV latency -- essentially, when HIV virus goes dormant and hides in host cells after initial infection -- is an especially important topic in developing a treatment since this allows the virus to evade the immune system and therapeutics. Current hypotheses of HIV latency have suggested that it is controlled by the environment and cellular state of the host cell, which naturally "relaxes" and suppresses the virus. In this first paper, however, Razooky et al demonstrate that HIV expression persists despite the transition in cellular state -- suggesting that the virus itself has programmed latency. Using synthetic biology, they were able to decoupling viral transcription from viral dependence on the environment in simplified circuits and show that the latency program is indeed hardwired into the virus.


But why employ this strategy? The second paper discusses the evolutionary advantages of such a system. Using computer simulation to verify their predictions, they asserted that this latency could be a "bet-hedging" strategy. If viral particles killed all their infected cells in an early stage of infection, the potential population of host cells would be eliminated -- by remaining latent, virus could lay in waiting until in an area of more potential target cells presents itself. 


These findings have turned the traditional views of HIV around, and will certainly contribute to the development of more sophisticated treatments that can break through the latency barrier that has prevented a cure in the past.


Graphical abstract from Rouzine et al, Cell