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

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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.

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Acknowledgments

The authors thank Sebastien Bontems and Catherine Sadzot-Delvaux (Liège, Belgium) for the generous gift of the VZV IE63 mAb; Susanne Bailer (Munich, Germany) for providing the VZV-infected MeWo cells; and Freek van Loenen (Rotterdam, The Netherlands) for technical assistance with the ABO blood group genotyping. This study was supported by a grant from the BMBF (German Ministry for Education and Research) IFB-01EO0901 to K.H.

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Authors and Affiliations

  1. Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands

    Werner J. D. Ouwendijk, Albert D. M. E. Osterhaus & Georges M. G. M. Verjans

  2. Department of Neurology, Ludwig-Maximilians University, Marchioninistr. 23, 81377, Munich, Germany

    Sarah E. Flowerdew, Desiree Wick, Michael Strupp & Katharina Hüfner

  3. Integrated Research and Treatment Center for Vertigo IFBLMU, Ludwig-Maximilians University, Munich, Germany

    Sarah E. Flowerdew, Desiree Wick, Anja K. E. Horn, Michael Strupp & Katharina Hüfner

  4. Institute of Anatomy, Department I, Ludwig-Maximilians University, Munich, Germany

    Anja K. E. Horn

  5. Department of Legal Medicine, Ludwig-Maximilians University, Munich, Germany

    Inga Sinicina

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  1. Werner J. D. Ouwendijk
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  2. Sarah E. Flowerdew
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  3. Desiree Wick
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  7. Albert D. M. E. Osterhaus
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  8. Georges M. G. M. Verjans
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  9. Katharina Hüfner
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Correspondence to Katharina Hüfner.

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Werner J. D. Ouwendijk and Sarah E. Flowerdew contributed equally to the manuscript.

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Ouwendijk, W.J.D., Flowerdew, S.E., Wick, D. et al. Immunohistochemical detection of intra-neuronal VZV proteins in snap-frozen human ganglia is confounded by antibodies directed against blood group A1-associated antigens. J. Neurovirol. 18, 172–180 (2012). https://doi.org/10.1007/s13365-012-0095-0

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