Temporal gate model.

<p>Virion delivered M45 and PRR signalling activate NFκB and other TFs downstream of TLRs, leading to transcription of innate immune effectors and viral IE-gene expression. Temporal gate open: In a <i>naiive</i> cell, viral infection triggers innate immune effector expression but at the same time drives viral gene expression. By the time host innate immune effectors are produced and can act on the viral IE-gene expression and replication, the virus already has progressed through this checkpoint of replication, produced viral inhibitors of innate immune signalling such as UL26, M27 or M45 and, using this lag-phase, escapes host control. Temporal gate closed: In a non-<i>naiive</i>, immune stimulated cell, the anti-viral effectors are already active at the point of infection and directly inhibit viral IE-gene expression. The viral gene expression cannot effectively progress beyond the IE-phase and the viral infection is controlled; the temporal gate is therefore closed.