Cell Intrinsic Determinants of Alpha Herpesvirus Latency and Pathogenesis in the Nervous System

Abstract

Alpha herpesvirus infections (α-HVs) are widespread, affecting more than 70% of the adult human population. Typically, the infections start in the mucosal epithelia, from which the viral particles invade the axons of the peripheral nervous system. In the nuclei of the peripheral ganglia, α-HVs establish a lifelong latency and eventually undergo multiple reactivation cycles. Upon reactivation, viral progeny can move into the nerves, back out toward the periphery where they entered the organism, or they can move toward the central nervous system (CNS). This latency–reactivation cycle is remarkably well controlled by the intricate actions of the intrinsic and innate immune responses of the host, and finely counteracted by the viral proteins in an effort to co-exist in the population. If this yin-yang- or Nash-equilibrium-like balance state is broken due to immune suppression or genetic mutations in the host response factors particularly in the CNS, or the presence of other pathogenic stimuli, α-HV reactivations might lead to life-threatening pathologies. In this review, we will summarize the molecular virus–host interactions starting from mucosal epithelia infections leading to the establishment of latency in the PNS and to possible CNS invasion by α-HVs, highlighting the pathologies associated with uncontrolled virus replication in the NS.

Advances in the immunoescape mechanisms exploited by alphaherpesviruses

“…The involvement of viral genetic material in the reactivation process is primarily examined from two perspectives. There is indeed a correlation between the viral load and the frequency and severity of recurrent lesions ( Salazar et al, 2023 ). In a mouse model, both the quantity of viruses and the frequency of lesions are contingent upon the amount of virus present at the time of vaccination.…”

Spatiotemporal regulation of Pseudorabies Virus Thymidine kinase UL23 by post-translational modification

“…Not only agricultural experts but also neurobiologists and virologists have shown a great interest in the study of the pseudorabies virus 7 . PRV has been used as a model virus for studying the molecular biology of the human herpesvirus HSV-1 8 . The UL23 protein is a thymidine kinase 9 that catalyzes the synthesis of viral DNA, participates in virus replication, and the spread of the virus in the central nervous system 10 .…”