Current In Vivo Models of Varicella-Zoster Virus Neurotropism

Abstract

Varicella-zoster virus (VZV), an exclusively human herpesvirus, causes chickenpox and establishes a latent infection in ganglia, reactivating decades later to produce zoster and associated neurological complications. An understanding of VZV neurotropism in humans has long been hampered by the lack of an adequate animal model. For example, experimental inoculation of VZV in small animals including guinea pigs and cotton rats results in the infection of ganglia but not a rash. The severe combined immune deficient human (SCID-hu) model allows the study of VZV neurotropism for human neural sub-populations. Simian varicella virus (SVV) infection of rhesus macaques (RM) closely resembles both human primary VZV infection and reactivation, with analyses at early times after infection providing valuable information about the extent of viral replication and the host immune responses. Indeed, a critical role for CD4 T-cell immunity during acute SVV infection as well as reactivation has emerged based on studies using RM. Herein we discuss the results of efforts from different groups to establish an animal model of VZV neurotropism.

Viral infections and multiple sclerosis

“…Moreover VZV infection is associated with higher risk of developing MS [102]. However appropriate animal models for the study of a role in MS are lacking, despite some attempts for the study of VZV neurotropism [103].…”

Intratracheal inoculation of human varicella zoster virus (VZV; MAV strain) vaccine successfully induced VZV IgG antibodies in rhesus monkeys

“…In the future, SVV can be obtained from leaders in the SVV field for the needed challenge studies. However, because various studies, especially Meyer et al’s report [ 3 ], have confirmed cross-reactive epitopes between SVV and VZV [ 6 – 8 ], it might be enough to show only the seropositivity of VZV IgG in rhesus monkeys. Although there were no comparators, such as a subcutaneously administered group and a intratracheal inoculation administered group, at the group-setting stage, our vaccination strategy produced a strong positive VZV IgG response in all vaccinated animals and suggests further testing.…”

Twelve Children with Varicella Vaccine Meningitis: Neuropathogenesis of Reactivated Live Attenuated Varicella Vaccine Virus

“…To date, the cases described in Table 1 and Table 2 gave a history of herpes zoster proceeding or concomitant with onset of symptoms of acute meningitis. After review of prior models [ 19 ], we propose a pathogenesis model ( Figure 4 ). Every child around the age of 1 year is given an initial injection of the live attenuated varicella vaccine in the thigh ( Figure 4 A).…”