Varicella Zoster: Virus and Disease


Varicella‐zoster virus (VZV) is a human‐specific virus that causes varicella (chickenpox) upon primary infection of children. During the convalescent stage of infection, VZV establishes latency in dorsal root ganglia of the nervous system and reactivates decades later in adults, causing herpes zoster (shingles). In the early 1970s, a live attenuated varicella vaccine was developed; subsequent varicella vaccination has greatly reduced VZV‐related hospitalisations and fatalities, although VZV remains commonplace in areas of the world that have not achieved high degrees of vaccination. VZV research continues to study viral mechanisms and pathogenesis. Recent experiments have discovered that VZV induces the cellular process called autophagy, which can aid in prolonging cell lifespan. Phylogenetic analyses of sequenced genomes indicate that the VZV genome originated in Africa and has coevolved with its human hosts during their migration out‐of‐Africa throughout the world.

Key Concepts:

  • Varicella‐zoster virus causes chickenpox initially, but remains latent in the body and can be reactivated, usually in the elderly, to cause the infection known as shingles.

  • VZV is one of nine human herpesviruses; in 2012, human herpesvirus type 6 was separated into two species called A and B. VZV is evolutionarily closely most related to the herpes simplex virus (HSV); however, it causes chickenpox and shingles and cannot cause herpes.

  • The double‐stranded DNA genome of VZV has been fully sequenced and has more than 70 open reading frames that encode nearly 70 unique proteins.

  • A highly geometrical and complex layer of proteins known as the capsid serves as a protective housing for the viral DNA; the capsid is then covered by a tegument and a lipid bilayer called the envelope.

  • Glycoproteins – proteins with bound sugars – are embedded within the envelope and serve functions from attachment to the host cell and cell‐to‐cell spread of the infection.

  • VZV is thought to have originated in Africa and has spread throughout the world by coevolving with its human host.

  • VZV is spread only during active infection; among the human herpesviruses, VZV is the only one that is spread by aerosolizing into airborne particles.

  • Autophagy, the recycling of damaged organelles, is induced by VZV as a method of prolonging cell lifespan, which gives the virus more time to replicate.

  • A live attenuated varicella vaccine was developed in the early 1970s and has dramatically reduced the number of VZV‐related hospitalisations and fatalities.

  • Antiviral drugs such as aciclovir are very effective in the treatment of VZV infections.

Keywords: varicella‐zoster virus; chickenpox; herpes zoster; shingles; human herpes virus; autophagy; vaccine; aciclovir

Figure 1.

Structure of the Varicella‐zoster virus (VZV) particle. (Left) The DNA genome (not shown) is found in the core of the viral particle. Surrounding the DNA is a protective layer of highly organised proteins known as the capsid (blue). The capsid is covered by another less geometric and less rigid layer of proteins called the tegument (dark purple). Proteins in the tegument aid in viral replication and evasion from the host immune system. The outermost covering of the viral particle is a lipid bilayer called the envelope (yellow). Embedded within the envelope are several glycoproteins (red, orange and pink) that are important in attachment to host cells and cell‐to‐cell spread. (Right) The capsid is arranged as an icosahedron, a 20‐sided structure. One face is enlarged to show the arrangement of proteins within the structure. The capsid is composed of proteins arranged into hexons (blue florets) that line the edges and faces, pentons (green florets) that are found at the vertices, and triplexes (orange points) that hold the hexons together. At one vertex, a dodecameric protein complex known as the portal (red floret) serves as an opening that allows packaging of the newly replicated viral DNA from the host nucleus into the capsid.

Figure 2.

Phylogeography of varicella‐zoster virus (VZV). VZV DNA samples collected from patients with active VZV infections from around the world were sequenced and compared. Single‐nucleotide polymorphisms (SNPs) were used to group strains of VZV into phylogenetic clades. Based on these phylogenetic experiments, VZV is thought to have originated in Africa and has coevolved with its human host during their migration throughout the world. To date, five distinct clades have been identified. Clades 1, 3 and 4 are predominantly in Europe as well as North America. Clade 5 is found mainly in VZV strains from people in India, whereas Clade 2 is predominantly found in China and Japan.



Arvin AM (2006) Investigations of the pathogenesis of Varicella zoster virus infection in the SCIDhu mouse model. Herpes 13: 75–80.

Breuer J, Grose C, Norberg P, Tipples G and Schmid DS (2010) A proposal for a common nomenclature for viral clades that form the species varicella‐zoster virus: summary of VZV Nomenclature Meeting 2008, Barts and the London School of Medicine and Dentistry, 24–25 July 2008. Journal of General Virology 91: 821–828.

Brunell PA and Gershon AA (1973) Passive immunization against varicella‐zoster infections and other modes of therapy. Journal of Infectious Diseases 127: 415–423.

Buckingham EM, Carpenter JE, Jackson W and Grose C (2014) Autophagy and the effects of its inhibition on varicella‐zoster virus glycoprotein biosynthesis and infectivity. Journal of Virology 88: 890–902.

Chow VT, Tipples GA and Grose C (2012) Bioinformatics of varicella‐zoster virus: single nucleotide polymorphisms define clades and attenuated vaccine genotypes. Infection Genetics and Evolution 18: 351–356.

Davison AJ and Scott JE (1986) The complete DNA sequence of varicella‐zoster virus. Journal of General Virology 67: 1759–1816.

Gershon AA, Arvin AM, Levin MJ, Seward JF and Schmid DS (2008) Varicella vaccine in the United States: a decade of prevention and the way forward. Journal of Infectious Diseases 197(suppl. 2): S39–S40.

Gilden DH, Gesser R, Smith J et al. (2001) Presence of VZV and HSV‐1 DNA in human nodose and celiac ganglia. Virus Genes 23: 145–147.

Grose C (1981) Variation on a theme by Fenner: the pathogenesis of chickenpox. Pediatrics 68: 735–737.

Grose C (1990) Glycoproteins of varicella‐zoster virus and their herpes simplex homologs. Reviews of Infectious Disease 13: S960–S963.

Grose C (2005) Varicella vaccination of children in the United States: assessment after the first decade 1995–2005. Journal of Clinical Virology 33: 89–95.

Grose C (2010) Autophagy during common bacterial and viral infections of children. Pediatric Infectious Disease Journal 29: 1040–1042.

Grose C (2012) Pangaea and the out‐of‐Africa model of varicella‐zoster virus evolution and phylogeography. Journal of Virology 86: 10695–10703.

Grose C and Wiedeman J (1997) Generic acyclovir vs. famciclovir and valacyclovir. Pediatric Infectious Disease Journal 16: 838–841.

Hope‐Simpson RE (1965) The nature of herpes zoster: a long‐term study and a new hypothesis. Proceedings of the Royal Society Medicine 58: 9–20.

Koshizuka T, Ota M, Yamanishi K and Mori Y (2010) Characterization of varicella‐zoster virus‐encoded ORF0 gene‐comparison of parental and vaccine strains. Virology 405: 280–288.

McGeoch DJ, Rixon FJ and Davison AJ (2006) Topics in herpesvirus genomics and evolution. Virus Research 117: 90–104.

Oxman MN, Levin MJ, Johnson GR et al. (2005) A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. New England Journal of Medicine 352: 2271–2284.

Peters GA, Tyler SD, Carpenter JE et al. (2012) The attenuated genotype of Varicella‐zoster virus includes an ORF0 transitional stop codon mutation. Journal of Virology 86: 10695–10703.

Peters GA, Tyler SD, Grose C et al. (2006) A full‐genome phylogenetic analysis of varicella‐zoster virus reveals a novel origin of replication‐based genotyping scheme and evidence of recombination between major circulating clades. Journal of Virology 80: 9850–9860.

Quinlivan M and Breuer J (2005) Molecular and therapeutic aspects of varicella‐zoster virus infection. Expert Reviews in Molecular Medicine 7: 1–24.

Roizman B and Knipe DM (2001) Herpes simplex viruses and their replication. In: Knipe DM, Howley PM, Griffin DE, et al. (eds) Fields Virology, pp. 2399–2459. Philadelphia: Lippincott.

Ross AH (1962) Modification of chicken pox in family contacts by administration of gamma globulin. New England Journal of Medicine 267: 369–376.

Takahashi M (2004) Effectiveness of live varicella vaccine. Expert Opinion on Biological Therapy 4: 199–216.

Tyler SD, Peters GA, Grose C et al. (2007) Genomic cartography of varicella‐zoster virus: a complete genome‐based analysis of strain variability with implications for attenuation and phenotypic differences. Virology 359: 447–458.

Weller TH (1983) Varicella and herpes zoster. Changing concepts of the natural history, control, and importance of a not‐so‐benign virus. New England Journal of Medicine 309: 1434–1440.

Further Reading

Gershon AA and Gershon MD (2013) Pathogenesis and current approaches to control of varicella‐zoster virus infections. Clinical Microbiology Review 26: 728–743.

Grose C and Adams HP (2014) Reassessing the link between herpes zoster ophthalmicus and stroke. Expert Review of Anti‐Infective Therapy 12: 527–530.

Quinlivan M and Breuer J (2014) Clinical and molecular aspects of the live attenuated Oka varicella vaccine. Review of Medical Virology 24: 254–273.

Zerboni L, Sen N, Oliver SL and Arvin AM (2014) Molecular mechanisms of varicella zoster virus pathogenesis. Nature Review of Microbiology 12: 197–210.

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Dotzler, Steven M, and Grose, Charles(Dec 2014) Varicella Zoster: Virus and Disease. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0020715.pub2]