Detection of herpes simplex virus (types 1 and 2) and human herpesvirus 6 DNA in human brain tissue by polymerase chain reaction

Abstract

Background: Previous studies, using a variety of techniques to determine whether herpes simplex virus type 1 (HSV-1) and/or type 2 (HSV-2) are present in normal brains or have a higher incidence in either multiple sclerosis (MS) or psychiatric disorders have yielded conflicting results. Similarly, studies to examine human brain tissue for human herpes virus 6 (HHV-6) have also proved inconsistent. These discrepancies may be partially due to differences in sensitivity of the methods used. Objectives: To determine whether: (i) Herpesvirus latency is a normal occurrence in the human central nervous system (CNS), (ii) the incidence of latency is higher in either demyelinating diseases or schizophrenia (iii) significant virus reactivation occurs in demyelinating diseases. Study Design: Frozen brain tissue from 7 cases of MS/demyelinating disease, 6 cases of schizophrenia and 27 non-neurological and 3 neurological controls were examined by polymerase chain reaction (PCR) for the presence of HSV-1 DNA. Tissue from the above catagories (except schizophrenia) were also examined for HSV-2 and HHV-6 DNA. In situ hybridization (ISH) and immunocytochemistry (ICC) were carried out in formalin-fixed paraffin sections from selected HSV PCR positive cases, including a case of HSV encephalitis (HSE). Results: Cases from all groups were found to be positive for HSV-1 by PCR. Only one case (MS) was found positive for HSV-2, whereas HHV-6 DNA was present in 18 of 23 brains (MS and controls). Only the HSE case gave positive results with ISH and ICC techniques. Conclusions: These results suggest that herpesvirus latency in the human CNS is a common occurrence but there is no obvious correlation with increased incidence in either demyelinating disease or schizophrenia. Furthermore, failure to detect virus by ISH or ICC (except in a case of HSE) indicates lack of any significant virus reactivation in demyelinating diseases.