VZV: Pathogenesis and the disease consequences of primary infection

Introduction VZV is a human alphaherpesvirus that causes varicella (chickenpox) as the primary infection and establishes latency in sensory ganglia. VZV reactivation results in herpes zoster (shingles). During the course of varicella and zoster, VZV infects differentiated human cells that exist within unique tissue microenvironments in humans. The tropism of VZV for skin is the most obvious clinical manifestation of VZV infection, producing the vesicular cutaneous lesions that are associated with varicella and zoster. The site of initial VZV infection in nave hosts is thought to be mucosal epithelial cells of the upper respiratory tract. Entry is presumed to follow inoculation of the respiratory epithelium with infectious virus transmitted by aerosolized respiratory droplets or by contact with virus in varicella or zoster skin lesions (Arvin, 2001a; Grose, 1981). VZV in respiratory or conjunctival mucosal cells has the opportunity to interact with and infect local immune system cells and those in adjacent lymphoid tissues. Trafficking of infected peripheral blood mononuclear cells (PBMC), which appear to be predominantly T-cells, to the skin is thought to give rise to crops of cutaneous vesicles. Skin lesions contain VZV material associated with necrotic debris and, unlike virus grown in vitro, cell-free, infectious particles are detected in vesicular fluid (Williams et al., 1962). The life cycle of VZV is completed upon its transmission to a susceptible host from an individual with varicella, or it can be postponed for decades by establishing latency in neurons and transmitting to future generations during episodes of zoster.