A Viral-Encoded Latency Program
Through a series of papers (Weinberger et al Cell 2005; Weinberger et al. Nature Gen 2007; Razooky et al. Cell 2015; Rouzine et al. Cell 2015; Hansen et al Cell 2018) we identified and characterized the function of an intrinsic (viral encoded) latency circuit in HIV.
HIV’s ability to establish a long-lived dormant-like state (called “proviral latency”) is the chief barrier to a cure. However, latency was generally believed to be an “epiphenomenon” resulting from epigenetic silencing during transitioning from activated to resting-memory cells and thought to play no role in the natural evolutionary history of the virus. Our studies overturned showed that HIV latency is a viral-encoded ‘bet-hedging’ program driven by HIV’s Tat gene-regulatory circuit (Razooky et al. 2015).
Partly, latency was thought to be an epiphenomenon because no evolutionary benefit had been proposed for the latent state. (modern ART did not influence viral evolution and HIV mutates quickly enough to evade immune responses, so unlike herpesviruses, no latent reservoir was needed). Our studies showed that a viral-encoded latency program enables early virus transmission and protects against viral extinction in target poor environments, e.g. the mucosa (Rouzine et al. 2015).
For review see:
Weinberger and Weinberger, Cell 2013.
Papers of note: Razooky, Pai et al. Cell 2015 (linked above) and Rouzine et al. Cell 2015.