Varicella zoster virus (VZV) is pathogenic. It is a well-established human pathogen that causes two distinct diseases: chickenpox (varicella) during the initial infection and shingles (herpes zoster) when the virus reactivates later in life. Humans are its only natural reservoir, and it spreads through direct contact with skin lesions or respiratory secretions.
How VZV Infects the Body
Primary infection begins when virus particles reach the epithelial cells lining the upper respiratory tract. The virus replicates locally, then spreads to the tonsils and nearby lymphoid tissues. From there, it hitches a ride on T cells, which carry it through the bloodstream to the skin. This journey explains the 10 to 21 day gap between exposure and the appearance of the characteristic chickenpox rash.
Once inside a cell, VZV hijacks the cell’s own machinery to reproduce. New virus particles appear on cell surfaces within about 12 hours of infection. Unlike many other herpesviruses, VZV stays tightly bound to the cells it infects rather than releasing free-floating particles. It also fuses infected cells with neighboring uninfected ones, creating large multi-nucleated cell clusters that help the virus spread from cell to cell without fully exposing itself to the immune system.
Two Diseases From One Virus
Chickenpox, the primary infection, starts on the face and scalp before spreading to the trunk and the rest of the body. The rash appears as scattered rose-colored spots that progress through several stages: flat marks, raised bumps, fluid-filled blisters, pustules, and finally crusts. A hallmark of chickenpox is that lesions in all these different stages are present at the same time.
Shingles looks and behaves differently. Instead of spreading across the whole body, the rash is confined to one side and follows the path of a single nerve (a dermatomal distribution). It typically appears as grouped blisters on a red base, often accompanied by significant pain in that same nerve’s territory. In people with weakened immune systems, shingles can disseminate more widely, but the unilateral, band-like pattern is the classic presentation.
Where the Virus Hides
After causing chickenpox, VZV doesn’t leave the body. It travels along nerve fibers and settles into clusters of nerve cells called ganglia, where it enters a dormant state known as latency. The primary hiding spots are the dorsal root ganglia along the spine and the cranial nerve ganglia in the head. Research has also identified a less well-known site: the enteric nervous system, the network of neurons lining the gut. Most human intestinal specimens examined in studies contained latent VZV within these intestinal nerve cells.
The virus reaches these locations through two routes. It can travel backward along nerve fibers from the skin (retrograde axonal transport), and it can arrive via the bloodstream during the initial infection. Once latent, VZV produces very little viral material, essentially hiding from the immune system. In roughly 30% of people who had chickenpox, the virus eventually reactivates to cause shingles. The main risk factor for reactivation is a decline in immune function, whether from aging, illness, or immunosuppressive medications.
Complications of Reactivation
The most common complication of shingles is postherpetic neuralgia (PHN), a condition in which chronic nerve pain persists for more than three months after the rash clears. People with PHN describe burning, aching, or lancinating pain along the area where the rash appeared, and even light touch on the skin can be painful. PHN can last months or years, and while antiviral medications may reduce its severity, no treatment reliably prevents it.
When VZV reactivates in cranial nerves, it can cause more specialized problems. Reactivation involving the nerve that supplies the eye can threaten vision. Reactivation in the nerve near the ear, known as Ramsay Hunt syndrome, can cause a blistering rash on the ear or inside the mouth, facial paralysis, hearing loss, and vertigo.
Treatment Timing Matters
Antiviral medications work best when started early. For shingles, beginning treatment within 72 hours of the rash appearing reduces viral shedding, speeds up skin healing, and limits pain duration. Patients who are older, have more extensive rashes, or are in significant pain may still benefit from treatment started after that 72-hour window, but once all lesions have crusted over, antivirals are unlikely to help.
For chickenpox, the window is even tighter. In otherwise healthy children, antiviral treatment provides meaningful benefit only when started within 24 hours of the rash. Adolescents and adults, who face a higher risk of complications from chickenpox, may benefit from treatment started up to 48 to 72 hours after onset.
Vaccine Protection
The recombinant shingles vaccine (Shingrix) is over 90% effective at preventing shingles and PHN in adults 50 and older with healthy immune systems. In clinical data, it was 97% effective in adults aged 50 to 69 and 91% effective in those 70 and older. For PHN specifically, effectiveness was 91% in adults over 50 and 89% in those over 70. In people with weakened immune systems, protection ranged from 68% to 91% depending on the underlying condition.
How VZV Is Confirmed in the Lab
PCR testing of skin lesion samples, ideally scabs, blister fluid, or cells scraped from the base of a lesion, is the most reliable way to confirm a VZV infection. It works well for both vaccinated and unvaccinated individuals. Older methods like direct fluorescent antibody testing and viral culture are less sensitive. Blood-based antibody tests (serology) can support a diagnosis, but they are considerably less sensitive than PCR from skin lesions. Paired blood samples showing a fourfold rise in antibody levels have excellent specificity, but PCR remains the gold standard.