SGM Journals

Research explained · Herpesvirus latency

What happens to HSV-1 DNA when the virus goes quiet?

Herpes simplex virus type 1 (HSV-1) left linear DNA in lab-grown, nerve-like cells for as long as 2 to 3 weeks after infection. The DNA persisted even after the researchers could no longer detect viral gene activity. At 3 to 4 weeks after infection with wild-type HSV-1, most of the inactive viral DNA had no detectable ends. [1]

See original studies View the SGM research record

What the researchers found at different points in the experiment

Inside a virus particle
HSV-1 carries a linear DNA molecule with two ends in the particle.
Inside cells, the researchers used detectable DNA ends as a sign of a linear genome. [1]
Up to 2 to 3 weeks in culture
Linear DNA persisted in the nuclei of PC12 cells treated with nerve growth factor. The DNA lay outside viral protein shells.
The cells could retain this form of DNA after viral gene activity fell below detection. [1]
Three to four weeks after wild-type infection
Most quiescent viral DNA had no free ends the test could detect.
The researchers tracked the mix of DNA forms in the cultures. They could not follow the fate of each molecule. [1]

Why use nerve-like cells?

The team treated PC12 cells with nerve growth factor to give them neuron-like characteristics. They followed the viral DNA after infection with either wild-type HSV-1 or a replication-defective strain. The timings come from those cells in culture. The study did not measure how long these forms persist in human nerves. [1][2]

What did studies of nerve tissue find?

In a separate study, researchers detected a DNA fragment consistent with joined HSV DNA ends in tissue from latently infected mice. They did not detect free ends, and they found a similar pattern in human nerve tissue. The PC12 experiment adds a timeline from a lab model. [1][2]

What does silence mean in this experiment?

Gene activity and the presence of viral DNA were separate measurements. In this experiment, the test for gene activity turned negative while the DNA remained measurable. [1]

Original research

  1. Su et al. (2002), Journal of General Virology. Stability and circularization of herpes simplex virus type 1 genomes in quiescently infected PC12 cultures. Primary PC12 culture time-course study.
  2. Efstathiou et al. (1986), Journal of Virology. Detection of herpes simplex virus-specific DNA sequences in latently infected mice and in humans. Primary study of latent HSV DNA in mouse and human tissue.