Fig. 4.

Pathways of stimuli induced reactivation. Low-level temporal expression of lytic genes can lead to production of the transcription factor complex and efficient temporal expression of lytic genes. This low-level expression is normally inhibited by factors released from surrounding CD8⁺ T cells. Interferon-γ (IFN-γ) inhibits ICP0 expression and granzyme B (GrzB) cleaves the ICP4 protein required for efficient expression of lytic genes. Stimuli such as hormone imbalance and stress inhibit CD8⁺ T cell activity, which allows low-level lytic gene expression to continue. Lytic gene expression leads to assembly of viral components, release, and reactivation (right). Alternatively, stimuli such as UV light and physical trauma initiate gene transcription through apoptotic signals. Apoptotic signaling leads to uncoordinated expression of lytic genes and production of new infectious viruses and reactivation (left)