Characterization of the host immune response in human Ganglia after herpes zoster.
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.
Gowrishankar
Kavitha
K
Centre for Virus Research, Westmead Millennium Institute, Sydney, NSW, Australia.
Steain
Megan
M
Cunningham
Anthony L
AL
Rodriguez
Michael
M
Blumbergs
Peter
P
Slobedman
Barry
B
Abendroth
Allison
A
D000293:Adolescent; D000328:Adult; D000369:Aged, 80 and over; D005260:Female; D005724:Ganglia / Q000276:immunology* / Q000821:virology; D006562:Herpes Zoster / Q000150:complications* / Q000276:immunology / Q000821:virology; D014645:Herpesvirus 3, Human / Q000276:immunology / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D051474:Neuralgia, Postherpetic / Q000209:etiology / Q000276:immunology* / Q000821:virology; D009474:Neurons / Q000276:immunology / Q000821:virology