The pathogenesis of VZV infection can be modelled by infecting xenografts of human foetal tissues in mice with severe combined immunodeficiency (SCID)26, 27, 33. These experiments identify a hydrophobic domain that mediates ORF61 self-interaction. With advancing age or immunosuppression, cell-mediated immunity to VZV declines, and the virus reactivates to cause zoster (shingles), dermatomal distribution, pain, and rash. The exact pathogenesis of the inflammatory reaction leading to persistent ganglion damage is still poorly understood. VZV replication is similar to that of herpes simplex virus. In this review, we discuss recent studies that provided novel insight in both the virus and host factors involved in the three elementary stages of Varicellovirus infection in primates: primary infection, latency and reactivation. Universal vaccination adopted in many countries with a two-dose strategy has allowed to significantly reducing morbidity and mortality of this infectious disease.
Unlike its close cousin, HSV, VZV does not lyse infected cells, but rather remains cell associated. It also is more fusogenic than HSV. This information is reassuring for countries considering universal varicella vaccination. These observations suggest that gB modulates cell–cell fusion via an ITIM-mediated Y881 phosphorylation-dependent mechanism, supporting a unique concept that intracellular signaling through this gBcyt motif regulates VZV syncytia formation and is essential for skin pathogenesis. The lack of a non-primate animal model of VZV severely limits research into the immune response to the virus. This laboratory has published extensively on different aspects of VZV pathogenesis with a particular emphasis on VZV glycoprotein function.