Abstract

Infection with varicella zoster virus (VZV) causes varicella (chickenpox), which can be severe in immunocompromised individuals, infants and adults. Primary infection is followed by latency in ganglionic neurons. During this period, no virus particles are produced and no obvious neuronal damage occurs. Reactivation of the virus leads to virus replication, which causes zoster (shingles) in tissues innervated by the involved neurons, inflammation and cell death — a process that can lead to persistent radicular pain (postherpetic neuralgia). The pathogenesis of postherpetic neuralgia is unknown and it is difficult to treat. Furthermore, other zoster complications can develop, including myelitis, cranial nerve palsies, meningitis, stroke (vasculopathy), retinitis, and gastroenterological infections such as ulcers, pancreatitis and hepatitis. VZV is the only human herpesvirus for which highly effective vaccines are available. After varicella or vaccination, both wild-type and vaccine-type VZV establish latency, and long-term immunity to varicella develops. However, immunity does not protect against reactivation. Thus, two vaccines are used: one to prevent varicella and one to prevent zoster. In this Primer we discuss the pathogenesis, diagnosis, treatment, and prevention of VZV infections, with an emphasis on the molecular events that regulate these diseases. For an illustrated summary of this Primer, visit: http://go.nature.com/14xVI1

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Acknowledgements

J.B. receives funding from the National Institute for Health Research (NIHR) University College London (UCL)/University College London Hospitals NHS Foundation Trust (UCLH) Biomedical Research Centre, UK. J.I.C. is supported by the intramural research program of the National Institute of Allergy and Infectious Diseases, USA. R.J.C. is supported by grants NS082228 and AG032958 from the US National Institutes of Health (NIH). D.G. is supported by grants AG006127 and AG032958 from the NIH. C.G. is supported by grant AI89716 from the NIH. S.H. receives funding from the Sir Jules Thorn Charitable Trust. M.D.G. and A.A.G. receive funding from NIH R01 Grant DK 09394. M.N.O.'s work is partially supported by the James R. and Jesse V. Scott Fund for Shingles Research in the Veterans Medical Research Foundation. P.G.E.K. receives grant funding for research from the Wellcome Trust.

Author information

Affiliations

  1. Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, New York 10032, USA.

    • Anne A. Gershon
  2. Department of Infection and Immunity, University College London, UK.

    • Judith Breuer
  3. Medical Virology Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Massachusetts, USA.

    • Jeffrey I. Cohen
  4. Departments of Neurology and Microbiology and Immunology, University of Colorado School of Medicine, Aurora, Colorado, USA.

    • Randall J. Cohrs
    •  & Don Gilden
  5. Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, New York, USA.

    • Michael D. Gershon
  6. Division of Infectious Diseases/Virology, Children's Hospital, University of Iowa, Iowa City, Iowa, USA.

    • Charles Grose
  7. Primary Immunodeficiency Group, Institute of Cellular Medicine, Newcastle University Medical School, Newcastle upon Tyne, UK.

    • Sophie Hambleton
  8. Department of Neurology, Institute of Neurological Sciences, Southern General Hospital, Glasgow University, Glasgow, Scotland, UK.

    • Peter G. E. Kennedy
  9. Infectious Diseases Section, Medicine Service, Veterans Affairs San Diego Healthcare System, Division of Infectious Diseases, Department of Medicine, University of California San Diego School of Medicine, San Diego, California, USA.

    • Michael N. Oxman
  10. Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USA.

    • Jane F. Seward
  11. Research Foundation for Microbial Diseases, Osaka University, Suita, Osaka, Japan.

    • Koichi Yamanishi

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Contributions

Introduction (A.A.G.); Epidemiology (J.F.S. and J.B.); Mechanisms/pathophysiology (D.G., R.J.C., P.G.E.K. and M.G.); Diagnosis, screening and prevention (A.A.G., M.N.O. and K.Y.), Management (J.I.C. and S.H.); Quality of life (A.A.G.); Outlook (C.G); and overview of Primer (A.A.G.).

Competing interests

J.B., J.I.C., R.J.C., M.D.G., D.G., C.G., S.H., M.N.O. and J.F.S. declare no competing interests. A.A.G. declares service contracts from Merck to investigate the safety of VZV vaccines (identifying VZV in samples from patients with possible adverse reactions), chairs an independent data monitoring committee for GlaxoSmithKlines Phase III subunit glycoprotein E zoster vaccine trial, consults with Pfizer when invited, and has participated in an educational programme (supported by an unrestricted educational grant) on zoster for GlaxoSmithKline. P.G.E.K. has served on a scientific advisory board on zoster vaccination for Sanofi Pasteur MSD. Y.K. is Director General of the BIKEN foundation (The Research Foundation for Microbial Diseases of Osaka University), which produces varicella vaccines.

Corresponding author

Correspondence to Anne A. Gershon.

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DOI

https://doi.org/10.1038/nrdp.2015.16

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