Studies on the pathogenesis of neurological diseases associated with Varicella‐Zoster Virus

Abstract

Immunocytochemical techniques and in situ hybridization with three different Varicella-Zoster Virus (VZV)-specific RNA probes have been used to study the pathogenesis of VZV-associated neurological syndromes. Varicella-Zoster Virus antigens were not detected using the avidin-biotin peroxidase technique with a polyvalent anti-VZV antibody in any of the formalin-fixed tissue sections from eight cases of VZV-associated neurological disease (encephalitis, myelitis, ganglionitis); one case was immunosuppressed although inflammatory lesions were present. Intense labelling was detected within the inflammatory lesions in several representative VZV cases with a monoclonal antibody against Class II MHC antigens, whereas cases of Herpes Simplex Virus encephalitis and normal controls were not so labelled. Three VZV probes from open reading frames 62, 16 and 40, which show homology with the Herpes Simplex Virus immediate early 175 kd protein, the 65 kd DNA binding protein and the major capsid protein respectively, were used for in situ hybridization studies in these VZV tissues. Although the probes were able to detect VZV RNA in VZV-infected CV-1 and Flow 2002 cell cultures and formalin-fixed VZV skin biopsy sections, positive hybridization was not seen in any of the neurological cases studied. Thus neither VZV nucleic acid nor antigens were detected in any of the cases of VZV-associated neurological disease. It is proposed that the mechanism of neurological damage in the syndromes is immune-mediated, there being increased expression of Class II MHC antigens associated with persistent inflammation.