Viable herpes simplex virus type 1 and varicella‐zoster virus in the trigeminal ganglia of human cadavers

Abstract

Human herpes simplex virus type 1 (HSV-1) and varicella-zoster virus (VZV) were isolated in the bilateral trigeminal ganglia of 12 human cadavers with no history of herpes-related symptoms within 1-5 days of death. Sixteen trigeminal ganglia were subjected to explant culture by using Vero cells, but no cytopathogenic effects (CPE) were observed. However, when another eight trigeminal ganglia were placed in a cell strainer and kept from direct contact with Vero cells during culture, CPE were clearly apparent in all cultures. The amount of DNA in the culture supernatants of 16 trigeminal ganglia decreased over time; 12 and 9 of these samples were PCR-positive for HSV-1 and VZV, respectively. In new Vero cells inoculated with supernatants collected 2 days after culture initiation, immunofluorescence staining revealed HSV-1 and VZV in 6 and 5 of 8 trigeminal ganglia, respectively. HSV-1 and VZV DNA was detected in supernatants collected 3 and 7 days after culture initiation and in Vero cells collected after culture completion, but real-time PCR revealed the DNA amounts decreased over time. There was less VZV DNA than HSV-1 DNA. These results demonstrate that infective HSV-1 and VZV can be isolated in culture, and confirm that viable HSV-1 and VZV persist in human trigeminal ganglia for some time after death.

Post-mortem detection of six human herpesviruses (HSV-1, HSV-2, VZV, EBV, CMV, HHV-6) in trigeminal and facial nerve ganglia by PCR

“…HSV-1 is widespread throughout the world and establishes latency in sensory ganglia. In the study conducted by Saitoh et al (2013), the trigeminal ganglia obtained from 12 human cadavers submitted for forensic autopsy within 1–5 days of death were cultured over a layer of Vero cells in order to evaluate whether the virus in the ganglia of the cadavers could be reactivated. It was demonstrated that viable HSV-1 persists in human trigeminal ganglia for some time after death.…”

“…As most humans are supposedly infected with multiple herpesviruses, the risk of virus reactivation and possible complications, especially if immunosuppression occurs, is significant. Multiple studies have concentrated on the presence of HSV-1, HSV-2, and VZV in cranial nerve ganglia, but there is limited data about the occurrence of EBV, CMV, and HHV-6 in these ganglia (Saitoh et al, 2013; Motani et al, 2006; Richter et al, 2009; Hill et al, 2008; Vrabec & Payne, 2001; Inoue et al, 2010; Cohrs, Barbour & Gilden, 1996; Furuta et al, 1992, 1997; Hüfner et al, 2007). The aim of this study was to determine the distribution of six different herpesviruses: HSV-1, HSV-2, VZV, EBV, CMV, and HHV-6 in trigeminal and facial nerve ganglia of the individuals who died of independent causes.…”

A comparison of herpes simplex virus type 1 and varicella-zoster virus latency and reactivation

“…Whilst VZV reactivation in explants of human ganglia remains elusive (Plotkin et al, 1977), it is reasonable to assume that this could be achieved, when the appropriate experimental conditions that favour this process are discovered. There is one report of VZV reactivation from human ganglia that had been removed 1-5 days post-mortem (Saitoh et al, 2013), but this observation has not been confirmed. Furthermore, only minimal amounts of VZV DNA replication, presumably an event preceding virus reactivation, have Sloutskin et al, 2013;Yu et al, 2013).…”

Varicella-Zoster Virus and Herpes Simplex Virus 1 Can Infect and Replicate in the Same Neurons whether Co- or Superinfected

“…Furthermore, both VZV and HSV are widespread human pathogens, with about 60 to 90% of the population latently infected by both viruses by adulthood (19). It has been reported that both viruses can reside latently in the same trigeminal ganglion (19)(20)(21)(22), and evidence from in situ hybridization suggests the rare presence of both HSV1 and VZV genomes in the same cells (23). However, the ability of both viruses to productively infect the same neuron has not been investigated.…”