Varicella-zoster virus (VZV) is a neurotropic human alphaherpesvirus that
causes varicella upon primary infection, establishes latency in multiple
ganglionic neurons, and can reactivate to cause zoster. Live attenuated VZV
vaccines are available; however, they can also establish latent infections and
reactivate. Studies of VZV latency have been limited to the analyses of human
ganglia removed at autopsy, as the virus is strictly a human pathogen.
Recently, terminally differentiated human neurons have received much attention
as a means to study the interaction between VZV and human neurons; however,
the short life-span of these cells in culture has limited their application.
Herein, we describe the construction of a model of normal human neural
progenitor cells (NHNP) in tissue-like assemblies (TLAs), which can be
successfully maintained for at least 180 days in three-dimensional (3D)
culture, and exhibit an expression profile similar to that of human trigeminal
ganglia. Infection of NHNP TLAs with cell-free VZV resulted in a persistent
infection that was maintained for three months, during which the virus genome
remained stable. Immediate-early, early and late VZV genes were transcribed,
and low-levels of infectious VZV were recurrently detected in the culture
supernatant. Our data suggest that NHNP TLAs are an effective system to
investigate long-term interactions of VZV with complex assemblies of human
neuronal cells
