Abstract

All herpes viruses establish lifelong infections (latency) in their host, and herpes simplex viruses (HSVs) are highly prevalent worldwide. Recurrence of HSV infections contributes to significant disease burden in people and on rare occasion can be fatal. Cell culture models that recapitulate latent infection provide valuable insight on the host processes regulating viral establishment and maintenance of latency. More robust and rapid than infections in live animal studies, advancements in neuronal culture techniques have made the systematic analysis of viral reactivation mechanisms feasible. Only recently have human neuronal cell lines been available, but models in the natural host cell are a critical addition to the currently available models.

Highlights

  • Current Clinical OutlookThe significant global prevalence of herpes simplex viruses (HSVs) is largely due to the fact that a defining characteristic of the herpesviruses is lifelong infection

  • HSV-2 is most commonly spread by sexual contact [3], whereas HSV type·1 (HSV-1) is frequently acquired through oral secretions as a mucosal infection during early childhood [4], the epidemiology is changing such that many countries are seeing increasing sexually transmitted infections of HSV-1 [5]

  • The purpose of this review is to examine the different HSV latency cell-culture models currently available, highlighting the specific contributions and advantages of each model

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Summary

Introduction

The significant global prevalence of herpes simplex viruses (HSVs) is largely due to the fact that a defining characteristic of the herpesviruses is lifelong infection. The reactivation of latent HSV leads to recurring ulcerative blisters at the mucosal surfaces near the primary site of infection (orolabial or genital herpes) [6], but other painful lesions can occur as well [7]. Acyclovir and its derivatives inhibit viral replication and reduce the duration and severity of clinical signs These therapies do not prevent recurrence arising from the reactivation of the latent virus [18]. Molecular studies of viral reactivation mechanisms using in vivo models have been limited [26]. With recent advances in neuronal culturing techniques, in vitro cell culture models have emerged as powerful tools to study the molecular and genetic mechanisms of HSV latency and reactivation. The purpose of this review is to examine the different HSV latency cell-culture models currently available, highlighting the specific contributions and advantages of each model

HSV Life Cycle
Latency Cell Culture Models
Non-neuronal Culture Models
Non-Human Neuronal Culture Models
Human Neuronal Culture Models
Findings
Concluding Remarks and Future Directions
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