Three-Dimensional Normal Human Neural Progenitor Tissue-Like Assemblies: A Model of Persistent Varicella-Zoster Virus Infection

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.