Characterization of the Host Immune Response in Human Ganglia after Herpes Zoster
Tóm tắt
Varicella-zoster virus (VZV) causes varicella (chicken pox) and establishes latency in ganglia, from where it reactivates to cause herpes zoster (shingles), which is often followed by postherpetic neuralgia (PHN), causing severe neuropathic pain that can last for years after the rash. Despite the major impact of herpes zoster and PHN on quality of life, the nature and kinetics of the virus-immune cell interactions that result in ganglion damage have not been defined. We obtained rare material consisting of seven sensory ganglia from three donors who had suffered from herpes zoster between 1 and 4.5 months before death but who had not died from herpes zoster. We performed immunostaining to investigate the site of VZV infection and to phenotype immune cells in these ganglia. VZV antigen was localized almost exclusively to neurons, and in at least one case it persisted long after resolution of the rash. The large immune infiltrate consisted of noncytolytic CD8+T cells, with lesser numbers of CD4+T cells, B cells, NK cells, and macrophages and no dendritic cells. VZV antigen-positive neurons did not express detectable major histocompatibility complex (MHC) class I, nor did CD8+T cells surround infected neurons, suggesting that mechanisms of immune control may not be dependent on direct contact. This is the first report defining the nature of the immune response in ganglia following herpes zoster and provides evidence for persistence of non-latency-associated viral antigen and inflammation beyond rash resolution.
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Anderson, P., C. Nagler-Anderson, C. O'Brien, H. Levine, S. Watkins, H. S. Slayter, M. L. Blue, and S. F. Schlossman. 1990. A monoclonal antibody reactive with a 15-kDa cytoplasmic granule-associated protein defines a subpopulation of CD8+ T lymphocytes. J. Immunol.144:574-582.
Arvin, A. M. 2001. Varicella-zoster virus., p. 2731-2768. In D. M. Knipe and P. M. Howley (ed.), Fields virology, 4th ed. Lippincott, Williams and Wilkins., Philadelphia, PA.
Curr. Top. Microbiol. Immunol.
Cohen, J., and S. E. Straus. 2001. Varicella zoster virus and its replication, p. 2707-2730. In D. M. Knipe and P. M. Howley (ed.), Fields virology, 4th ed. Raven Press, New York, NY.
Denny-Brown, D., R. Adam, and P. Fitzgerald. 1944. Pathologic features of herpes zoster. AMA Arch. Derm.75:193-196.
Dworkin, R., and K. E. Schmader. 2001. Herpes zoster and post herpetic neuralgia, p. 39-64. In C. P. N. Watson and A. A. Gershon (ed.), The epidemiology and natural history of herpes zoster and postherpetic neuralgia, 2nd ed. Elsevier Press, New York, NY.
Gilden, D. H., R. Mahalingam, A. N. Dueland, and R. Cohrs. 1992. Herpes zoster: pathogenesis and latency. Progr. Med. Vir.36:19-75.
Gnann, J. 2008. Preventing herpes zoster. J. Pain9:S31-S36.
Hope-Simpson, R. E. 1975. Postherpetic neuralgia. J. R. Coll. Gen. Pract.25:571-575.
Kinchington, P., and J. I. Cohen. 2000. Varicella zoster virus proteins, p. 74-104. In A. Gershon (ed.), Varicella-zoster virus: virology and clinical management. Cambridge University Press, Cambridge, United Kingdom.
Kinchington, P. R. 1999. Latency of varicella zoster virus; a persistently perplexing state. Front. Biosci.4:D200-D211.
Lancaster, T., C. Silagy, and S. Gray. 1995. Primary care management of acute herpes zoster: systematic review of evidence from randomized controlled trials. Br. J. Gen. Pract.45:39-45.
Li, Q., N. Chen, J. Yang, M. Zhou, D. Zhou, Q. Zhang, and L. He. 2009. Antiviral treatment for preventing postherpetic neuralgia. Cochrane Database Syst. Rev.CD006866.
Varicella zoster virus: virology and clinical management 2000
Portenoy, R. K. 1986. Postherpetic neuralgia: a workable treatment plan. Geriatrics41:34-36, 47-48.
Sadzot-Delvaux, C., and B. Rentier. 2000. Animal models of infection, p. 169-186. In A. M. Arvin and A. A. Gershon (ed.), Varicella zoster virus; virology and clinical management. Cambridge University Press, Cambridge, United Kingdom.
The neuropathology of herpes zoster with particular reference to postherpetic neuralgia and its pathogenesis 1993 vol. 8
Wu, C. L., and S. N. Raja. 2008. An update on the treatment of postherpetic neuralgia. J. PainS19-S30.