Discovery reveals mechanism that turns herpes virus on and off

New research has identified a new mechanism that plays a role in controlling how the herpes virus alternates between dormant and active stages of infection.

The herpes virus causes cold sores and genital sores, as well as life-threatening infections in newborns, encephalitis and corneal blindness.

Treatment of the virus is difficult, because it hides out in nerve cells and emerges months or years later to reactivate the infection.

Researchers have discovered that the virus switches between the "latent" stage and the "lytic" stage, in which it is actively replicating, depending on how tightly its DNA is packaged into bundles called chromatin.

When the herpes virus enters a cell, the cell tries to protect itself by wrapping the viral DNA tightly around spool-like proteins called histones and condensing it into chromatin, which causes the virus to go dormant. But if the cells are unsuccessful, the chromatin is only loosely bundled, leaving the viral DNA accessible. The virus particles can then turn on their genes and replicate using the cell's machinery to start a lytic infection, causing disease.

The researchers showed that the dynamics of the chromatin regulate whether the entire herpes virus genome is turned on, which must occur before any individual genes can be expressed. This new mechanism represents a previously overlooked way to regulate gene expression at the level of the entire viral chromosome.

With this new knowledge, researchers can further explore the interplay between the virus and host cells that determines whether viral DNA is expressed. Antiviral drugs to treat herpes have existed since the 1960s, but thus far a cure or an effective vaccine has been out of reach.

The discovery opens up new directions for exploring how the virus reactivates after lying dormant. Herpes' ability to lay low has thwarted efforts to create effective vaccines or antiviral drugs that fully prevent or cure the infection.

See:

MiYao Hu, Daniel P. Depledge, Esteban Flores Cortes, Judith Breuer, Luis M. Schang. Chromatin dynamics and the transcriptional competence of HSV-1 genomes during lytic infections. PLOS Pathogens, 2019; 15 (11): e1008076 DOI: 10.1371/journal.ppat.1008076

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)