Journal of NeuroVirology

, Volume 18, Issue 3, pp 172–180

Immunohistochemical detection of intra-neuronal VZV proteins in snap-frozen human ganglia is confounded by antibodies directed against blood group A1-associated antigens

  • Werner J. D. Ouwendijk
  • Sarah E. Flowerdew
  • Desiree Wick
  • Anja K. E. Horn
  • Inga Sinicina
  • Michael Strupp
  • Albert D. M. E. Osterhaus
  • Georges M. G. M. Verjans
  • Katharina Hüfner
Article

DOI: 10.1007/s13365-012-0095-0

Cite this article as:
Ouwendijk, W.J.D., Flowerdew, S.E., Wick, D. et al. J. Neurovirol. (2012) 18: 172. doi:10.1007/s13365-012-0095-0

Abstract

Varicella-zoster virus (VZV) causes chickenpox, establishes latency in trigeminal (TG) and dorsal root ganglia (DRG), and can lead to herpes zoster upon reactivation. The VZV proteome expressed during latency remains ill-defined, and previous studies have shown discordant data on the spectrum and expression pattern of VZV proteins and transcripts in latently infected human ganglia. Recently, Zerboni and colleagues have provided new insight into this discrepancy (Zerboni et al. in J Virol 86:578–583, 2012). They showed that VZV-specific ascites-derived monoclonal antibody (mAb) preparations contain endogenous antibodies directed against blood group A1 proteins, resulting in false-positive intra-neuronal VZV staining in formalin-fixed human DRG. The aim of the present study was to confirm and extend this phenomenon to snap-frozen TG (n = 30) and DRG (n = 9) specimens of blood group genotyped donors (n = 30). The number of immunohistochemically stained neurons was higher with mAb directed to immediate early protein 62 (IE62) compared with IE63. The IE63 mAb-positive neurons always co-stained for IE62 but not vice versa. The mAb staining was confined to distinct large intra-neuronal vacuoles and restricted to A1POS donors. Anti-VZV mAb staining in neurons, but not in VZV-infected cell monolayers, was obliterated after mAb adsorption against blood group A1 erythrocytes. The data presented demonstrate that neuronal VZV protein expression detected by ascites-derived mAb in snap-frozen TG and DRG of blood group A1POS donors can be misinterpreted due to the presence of endogenous antibodies directed against blood group A1-associated antigens present in ascites-derived VZV-specific mAb preparations.

Keywords

Varicella-zoster virusSnap-frozen human sensory gangliaAscites-derived monoclonal antibodiesImmunohistochemistryFalse-positiveABO genotype A1

Copyright information

© Journal of NeuroVirology, Inc. 2012

Authors and Affiliations

  • Werner J. D. Ouwendijk
    • 1
  • Sarah E. Flowerdew
    • 2
    • 3
  • Desiree Wick
    • 2
    • 3
  • Anja K. E. Horn
    • 3
    • 4
  • Inga Sinicina
    • 5
  • Michael Strupp
    • 2
    • 3
  • Albert D. M. E. Osterhaus
    • 1
  • Georges M. G. M. Verjans
    • 1
  • Katharina Hüfner
    • 2
    • 3
  1. 1.Department of VirologyErasmus Medical CenterRotterdamThe Netherlands
  2. 2.Department of NeurologyLudwig-Maximilians UniversityMunichGermany
  3. 3.Integrated Research and Treatment Center for Vertigo IFBLMULudwig-Maximilians UniversityMunichGermany
  4. 4.Institute of Anatomy, Department ILudwig-Maximilians UniversityMunichGermany
  5. 5.Department of Legal MedicineLudwig-Maximilians UniversityMunichGermany