Viral protein VP16 prompts herpes simplex virus (HSV) to exit latency and cause recurrent disease, according to a team of researchers. They report the production of this protein in latently infected neurons, reactivates the virus and prompts new rounds of replication at the body surface.
HSV replicates itself at the body surface, and these copies that can be transmitted to other people. In neurons, however, the virus usually enter a silent state, where the viral genetic code can be maintained for the lifetime of the infected person.
The researchers conjecture that HSV usually remains latent because VP16, which normally enters the cell with the virus particle, does not make the long trip the virus takes through the nervous system and isn’t transported efficiently to the nerve cell nucleus.
Because fever has long been known to induce HSV reactivation, in this study the scientists simulated high fever in a mouse model. The research appears in PLoS Pathogens and is titled, “De Novo Synthesis of VP16 Coordinates the Exit from HSV Latency In Vivo.”
The scientists observed that though in the vast majority of neurons the virus remained latent, in a few the fever led to a stochastic de-repression of VP16, causing the virus to exit latency and reactivate.
“This completely changes our thinking about how this virus reactivates from latency,” according to Richard Thompson, Ph.D., researcher in the department of molecular genetics, biochemistry, and microbiology at the University of Cincinnati. “Instead of a simple positive switch that turns the virus on following stress, it appears instead to be a random de-repression of the VP16 gene that results in reactivation.”