Prevalence of HHV-6 in human sensory ganglia

Introduction: Herpesviruses such as herpes simplex virus type-1 (HSV-1) and varicella zoster virus (VZV) have the ability to persist for life in human sensory ganglia. When reactivated, they may cause a wide spectrum of clinical manifestations, ranging from asymptomatic viral shedding to fatal disease. Human herpes virus 6 (HHV-6) has recently been shown to persist in the central nervous system, but its prevalence in the peripheral nervous system (PNS) has not been studied.

Methods: Using nested PCR, we determined the distribution of HHV-6 and its co-localization with alpha-herpesviruses (HSV-1 and VZV) in ten human trigeminal (TG), 20 geniculate (GG), 20 vestibular (VG), and in 11 dorsal root ganglia (DRG). The presence of infiltrating T-cells in the respective ganglia was determined via immunohistochemistry.

Results: HHV-6 was present in 30% of the TG, 40% of the GG, 25% of the VG, and 55% of the DRG. It co-occurred with alpha-herpesviruses in 91% of the HHV-6 positive ganglia. Only two ganglia were solely positive for HHV-6 (9%). Chi-square statistics showed that the infection of a sensory ganglion with HHV-6 was associated with infection of another herpesvirus (either HSV-1 or VZV; p<0.01). The co-occurrence of HSV-1 and VZV in the ganglia was not statistically significant (p>0.01). The presence of HHV-6 did not correlate with the persistence of inflammatory cells, which are known to harbor HHV-6.

Conclusion: This study presents evidence that HHV-6 is prevalent in the peripheral nervous system. All the human sensory ganglia, e.g., TG, GG, VG, and DRG, can get infected with HHV-6. The lack of correlation between HHV-6 and inflammatory cells suggests that HHV-6 resides in human sensory ganglia themselves. It is possible that HHV-6 is the first of the herpesviruses to infect the ganglia, since infection occurs quite early, usually within the first year of life. In contrast, HSV-1 and VZV infections occur later. Latent HHV-6 could create an environment in the ganglia which facilitates the invasion of other viruses. In point of fact, it has been demonstrated that HHV-6 can interact with a number of other viruses during active infection, latency, and reactivation.