Herpesvirus reactivation

Herpesvirus reactivation is the biological process by which latent herpesviruses, such as Herpes Simplex Virus (HSV), Varicella-Zoster Virus (VZV), and Cytomegalovirus (CMV), transition from a dormant state to active lytic replication [2, 16]. This phenomenon occurs when the viral genome, which persists as an episome in host cells like neurons or B cells, is triggered by factors such as immunosuppression, physical stress, or systemic inflammation [2, 10]. Reactivation leads to the expression of immediate-early genes (e.g., RTA in KSHV or VP16 in HSV), followed by viral DNA synthesis and the assembly of new infectious virions [1, 5]. Clinically, this manifests as recurrent outbreaks, viral shedding, and potentially severe complications like encephalitis, retinitis, or post-herpetic neuralgia [7, 13]. Pharmacological intervention typically targets the viral machinery required for this transition, most notably the viral DNA polymerase, which is inhibited by nucleoside analogs like acyclovir and ganciclovir [4, 9]. Newer therapeutic classes, such as helicase-primase inhibitors (e.g., pritelivir) and terminase inhibitors (e.g., letermovir), provide alternative mechanisms to suppress reactivation by blocking different stages of the viral life cycle [9, 12]. Despite these treatments, current antivirals cannot eradicate the latent viral reservoir, making reactivation a lifelong risk for infected hosts [14, 15].

Other names

Viral recrudescenceLytic reactivationLatency escapeViral breakoutHerpesvirus lytic induction

Inhibition of viral DNA polymerase, viral terminase complex, helicase-primase complex, or viral protein kinases to prevent lytic replication.