Varicella-zoster virus (VZV), also known as human herpesvirus 3, is an enveloped double-stranded DNA virus that causes varicella (chickenpox) upon primary infection and herpes zoster (shingles) upon reactivation from latency. It belongs to the Alphaherpesvirinae subfamily and infects only humans.
Structure, replication cycle and latency
VZV has a linear double-stranded DNA genome of about 125 kilobases packaged within an icosahedral capsid surrounded by a tegument layer and a lipid envelope studded with glycoproteins. Infection begins when viral glycoproteins bind to cellular receptors, allowing fusion of the viral envelope with host cell membranes. The nucleocapsid is transported to the nucleus, where the viral genome circularizes and is transcribed by host RNA polymerase. Early and late gene products orchestrate DNA replication, capsid assembly and acquisition of the tegument and envelope. Progeny virions exit cells by exocytosis. During primary infection, VZV replicates in the respiratory mucosa, then disseminates via lymphatics and bloodstream to skin and other organs. Following resolution of varicella, the virus remains latent within cranial nerve, dorsal root and autonomic ganglia neurons, persisting as episomal DNA with minimal gene expression. Reactivation later in life, often triggered by immunosuppression or aging, results in anterograde transport of virus along sensory nerves to the skin, causing unilateral dermatomal vesicular eruptions characteristic of herpes zoster.
Diseases, complications and prevention
Varicella typically manifests as a febrile illness with a generalized pruritic vesicular rash in children; adults may experience more severe disease with pneumonitis or encephalitis. Congenital varicella syndrome can occur when infection arises during early pregnancy. Herpes zoster causes a painful localized rash in a single dermatome and may be followed by post-herpetic neuralgia, a chronic neuropathic pain that persists after lesions heal. Immunocompromised individuals are at risk for disseminated disease affecting multiple organs. Live attenuated varicella vaccines are used to prevent primary infection, and a more potent zoster vaccine reduces the risk of shingles and its complications in older adults. Antiviral drugs such as acyclovir, valacyclovir and famciclovir are used to treat severe or complicated cases. VZV exemplifies the ability of herpesviruses to establish lifelong latency and reactivate. Understanding its biology has informed vaccine development and management strategies that have substantially reduced the burden of chickenpox and shingles. Related Terms: Herpesvirus, Chickenpox, Shingles, Latency, Reactivation