Herpes simplex virus 1 (HSV-1) and varicella-zoster virus (VZV) cause serious central nervous system (
CNS) diseases that are diagnosed with PCR using samples of cerebrospinal fluid (CSF) and, during later stages of such
infections, with assays of intrathecal
IgG antibody production. However, serological diagnoses have been hampered by cross-reactions between HSV-1 and VZV
IgG antibodies and are commonly reported in patients with
herpes simplex encephalitis (HSE). In this study we have evaluated VZV
glycoprotein E (gE) as a new
antigen for serological diagnosis of VZV-induced
CNS infections. Paired samples of CSF and serum from 29 patients with clinical diagnosis of VZV
CNS infection (n = 15) or HSE (n = 14), all confirmed by PCR, were analyzed.
VZV gE and whole VZV were compared as
antigens in
enzyme-linked
immunosorbent assays (ELISAs) for serological assays in which the CSF/serum sample pairs were diluted to identical
IgG concentrations. With the gE
antigen, none of the HSE patients showed intrathecal
IgG antibodies against VZV, compared to those shown by 11/14 patients using whole-VZV
antigen (P < 0.001). In the patients with VZV
infections, significantly higher CSF/serum optical density (OD) ratios were found in the VZV patients using the
VZV gE antigen compared to those found using the whole-VZV
antigen (P = 0.001). These results show that gE is a sensitive
antigen for serological diagnosis of VZV
infections in the CNS and that this
antigen was devoid of cross-reactivity to HSV-1
IgG in patients with HSE. We therefore propose that
VZV gE can be used for serological discrimination of
CNS infections caused by VZV and HSV-1.