Productive vs non-productive infection by cell-free varicella zoster virus of human neurons derived from embryonic stem cells is dependent upon infectious viral dose

Varicella Zoster virus (VZV) productively infects humans causing varicella upon primary infection and herpes zoster upon reactivation from latency in neurons. In vitro studies using cell-associated VZV infection have demonstrated productive VZV-infection, while a few recent studies of human neurons derived from stem cells incubated with cell-free, vaccine-derived VZV did not result in generation of infectious virus.In the present study, 90%-pure human embryonic stem cell-derived neurons were incubated with recombinant cell-free pOka-derived virus made with an improved method or VZV vaccine. We found that cell-free pOka and vOka at higher multiplicities of infection elicited productive infection in neurons followed by spread of infection, cytopathic effect and release of infectious virus into the medium. These results further validate the use of this unlimited source of human neurons for studying unexplored aspects of VZV interaction with neurons such as entry, latency and reactivation.